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Dr Nikhil Dhurandhar John H Hernandez Professor in Health Promotion Louisiana State University
INFECTOBESITY Obesity of Infectious Origin
Nikhil V Dhurandhar
John H Hernandez Endowed Professor in Health Promotion
Infection and Obesity Laboratory
Pennington Biomedical Research Center
Louisiana State University System
Baton Rouge Louisiana
Salzburg Austria 2012
ldquoMost Obese persons will not stay in treatment for Obesity
Of those who stay in treatment most will not lose weight
and of those who do lose weight most will regain itrdquo
- Albert Stunkard 1958
EAT LESS MOVE MORE
TREATMENT VS RESEARCH
eg CANCER HIV
Just one big meal does not cause obesity
Just one small meal does not fix obesity
The search for
effective amp meaningful approaches
OBESITY
A complex disease with multi-factorial etiology
It requires a multi-factorial treatment and
prevention approach
CAUSE-SPECIFIC APPROACH
Different prevention amp treatment strategies
BETTER RESULTS
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
INFECTOBESITY Obesity of Infectious Origin
Nikhil V Dhurandhar
John H Hernandez Endowed Professor in Health Promotion
Infection and Obesity Laboratory
Pennington Biomedical Research Center
Louisiana State University System
Baton Rouge Louisiana
Salzburg Austria 2012
ldquoMost Obese persons will not stay in treatment for Obesity
Of those who stay in treatment most will not lose weight
and of those who do lose weight most will regain itrdquo
- Albert Stunkard 1958
EAT LESS MOVE MORE
TREATMENT VS RESEARCH
eg CANCER HIV
Just one big meal does not cause obesity
Just one small meal does not fix obesity
The search for
effective amp meaningful approaches
OBESITY
A complex disease with multi-factorial etiology
It requires a multi-factorial treatment and
prevention approach
CAUSE-SPECIFIC APPROACH
Different prevention amp treatment strategies
BETTER RESULTS
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
ldquoMost Obese persons will not stay in treatment for Obesity
Of those who stay in treatment most will not lose weight
and of those who do lose weight most will regain itrdquo
- Albert Stunkard 1958
EAT LESS MOVE MORE
TREATMENT VS RESEARCH
eg CANCER HIV
Just one big meal does not cause obesity
Just one small meal does not fix obesity
The search for
effective amp meaningful approaches
OBESITY
A complex disease with multi-factorial etiology
It requires a multi-factorial treatment and
prevention approach
CAUSE-SPECIFIC APPROACH
Different prevention amp treatment strategies
BETTER RESULTS
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
EAT LESS MOVE MORE
TREATMENT VS RESEARCH
eg CANCER HIV
Just one big meal does not cause obesity
Just one small meal does not fix obesity
The search for
effective amp meaningful approaches
OBESITY
A complex disease with multi-factorial etiology
It requires a multi-factorial treatment and
prevention approach
CAUSE-SPECIFIC APPROACH
Different prevention amp treatment strategies
BETTER RESULTS
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
TREATMENT VS RESEARCH
eg CANCER HIV
Just one big meal does not cause obesity
Just one small meal does not fix obesity
The search for
effective amp meaningful approaches
OBESITY
A complex disease with multi-factorial etiology
It requires a multi-factorial treatment and
prevention approach
CAUSE-SPECIFIC APPROACH
Different prevention amp treatment strategies
BETTER RESULTS
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Just one big meal does not cause obesity
Just one small meal does not fix obesity
The search for
effective amp meaningful approaches
OBESITY
A complex disease with multi-factorial etiology
It requires a multi-factorial treatment and
prevention approach
CAUSE-SPECIFIC APPROACH
Different prevention amp treatment strategies
BETTER RESULTS
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
The search for
effective amp meaningful approaches
OBESITY
A complex disease with multi-factorial etiology
It requires a multi-factorial treatment and
prevention approach
CAUSE-SPECIFIC APPROACH
Different prevention amp treatment strategies
BETTER RESULTS
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
OBESITY
A complex disease with multi-factorial etiology
It requires a multi-factorial treatment and
prevention approach
CAUSE-SPECIFIC APPROACH
Different prevention amp treatment strategies
BETTER RESULTS
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
CAUSE-SPECIFIC APPROACH
Different prevention amp treatment strategies
BETTER RESULTS
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Infections Endocrine disrupters Sleep debt
Pharmaceutical iatrogenesis Ambient temperature
Intrauterine and Intergenerational effects Epigenetics
Maternal age Assortative mating
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Is Obesity an infectious disease
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Is Gastric Ulcer an infectious disease
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Causes of gastric ulcer
Hurry
Worry
and Curry
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Photo httpenwikipediaorgwikiFileRobin_Warrenjpg
THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
Barry J Marshall J Robin Warren
ldquofor their discovery of the
Bacterium
Helicobacter pylori
and its role in
Gastritis and peptic
ulcer diseaserdquo
2005
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Obesity of infectious origin
INFECTOBESITY
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Significance of Infectobesity Research
1) Obesity has multifactorial etiology but the treatment
is not cause-specific
2) Specific prevention treatment strategies
3) Small pox eradication
INFECTOBESITY
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
httpwwwflickrcomcamerassonydsc-w55
UNIVERSITY OF MUMBAI
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Dhurandhar NV et al Vet Microbiol 1992 31 101-107
Dhurandhar NV et al Obesity Res 1997 5464-69
Dhurandhar NV et al J Bom Vet College 1990 2131-32
Chickens SMAM-1 increases adiposity amp reduced serum lipids
Obese Humans SMAM-1 is associated with greater BMI and lower lipids
AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982
2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999
7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
0
20
40
60
80
100
o
be
se
Obesity Prevelance
Control
Ad36
Dhurandhar et al Int J Obes 200125990-996
Dhurandhar et al J Nutr 2002 1323155-3160
Dhurandhar et al Int J Obes 200024989-996
Pasarica et al Obesity 2006 14 (11) 1905-13
AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
0
5
10
15
20
25
30
35
40
45
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks post inoculation
We
igh
t c
ha
ng
e (
g)
Ad-36
Control
0
4
8
12
16
Total Body Fat ()
Ad-36
Control
Weight change Body fat
AD-36 INCREASES ADIPOSITY IN MARMOSETS
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Virus-induced obesity
Mechanism of Action
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
STEM CELLS
ADIPOCYTE
PRE-
ADIPOCYTE
Mechanism of action of Ad36
Adipose tissue expansion by increasing proliferation
commitment differentiation and lipid accumulation in
adipocyte progenitors ASC
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Virus-induced obesity
A causative role in humans
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Challenges
1 Obesity has insidious onset
2 Multiple etiological factors ndash difficult to attribute to a factor
3 A combination of infection with other factors needed
4 Ethical reasons preclude experimental infection of humans
Do certain infections cause human obesity
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Twin Study
Body weight of twins is similar
Hypothesis
Ad36 infected co-twins will be heavier compared
to uninfected co-twins
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Twin pairs (n=26) discordant for Ad-36 antibodies
Antibody + Antibody -
Age (y) 330 plusmn 157 330 plusmn 157
Sex ( F M) 77 23 77 23
BMI (kgm2) 245 plusmn 52 231 plusmn 45
Body fat () 296 plusmn 95 275 plusmn 99
Int J Obesity 2005 29(3)281-6
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Exposure to Ad36 was associated with
a) greater fat at baseline
b) greater increase in fat
Lin WY et al Diabetes Care Nov 2012
Serum samples of 1400 Mexican American individuals
Longitudinal study ndash 10 y follow up
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Dhurandhar NV Lancet Inf Dis 2011 11963-69
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
USA
CA GA MD
MO (WI MI LA VA)
Canada Mexico
Korea China
Sweden Belgium
The Czech Republic
Italy Poland
Turkey
Australia
AD-36 STUDIES
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Ad36 amp BMI
Ad36 amp Obesity
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN
HUMANS
Obesity 2013 Jun 26 doi 101002oby20533
Serological data analyses show that adenovirus
36 infection is associated with obesity
A meta-analysis involving 5739 subjects
Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Virus-induced obesity
Implications
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Obesity Prevention amp
Treatment
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Na amp Nam JID 2012 205914
C57BL6 mice WT vs MCP1 KO mice
Ad36 up-regulates inflammatory cytokines in vivo
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub
ahead of print]
Reduction of adenovirus 36-induced obesity and inflammation via the
use of mulberry extract
Na HN1 Park S Jeon HJ Kim HB Nam JH
Mulberry extract reduces inflammation and Ad36-induced obesity
Treatment of Ad36-induced obesity
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Prevention of Ad36-induced obesity
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
SUMMARY amp CONCLUSION
OBESITY
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
SUMMARY amp CONCLUSION
OBESITIES
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
SUMMARY amp CONCLUSION
OBESITIES
Unique prevention amp treatment strategies for
Ad36-induced obesity
Other adipogenic pathogens
other types of ldquoobesitiesrdquo
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
A United States Patents approved
1 Number 6127113 Viral Obesity methods and Compositions
2 Number 6664050 Viral Obesity methods and Compositions
3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses
B Patents filed
1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic
fatty liver disease US patent application 61362443 Taiwan Patent number
100124173
2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
C Provisional patent filed
1 Compositions and methods for improving glucose uptake
PATENTS
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
National Institutes of Health
American Diabetes Association
Federal Emergency Management Agency
American Egg Board
The Mathile Institute
Vital Health Interventions
Kellogg
Genentech
Novartis
Hoffman La Roche
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Lei Cao Ohio State University NIH 121CA178227-01
Rena S Day University of Texas FEMA
Melinda Sothern NIH R01
Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal
Jae-Hwan Nam South Korea - proposal
COLLABORATIVE GRANTS ndash AD36 E4orf1
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD
Sharada Vangipuram PhD
Minghuan Yu MD PhD
Bhavani Krishnan MS
Mitali Kapila MS
John Sheele MS
Magdalena Pasarica MD PhD
Miloni Rathod MS
Pamela Rogers MS
Scott Loiler PhD
Nazar Mashtalir
Olga Dubuisson MD PhD
Emily McAllister
Rashmi Krishnapuram PhD
Heather Kirk-Ballard MS
COLLABORATORS CONTRIBUTORS
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Paige Kennedy
Olga Dubuisson MD PhD Rashmi Krishnapuram PhD
Grant Williams
SooHo Park
Ha-Na Na PhD
Jae-Hwan Nam PhD
Vijay Hegde PhD
Cathy Huey
INFECTIONS AND OBESITY LABORATORY
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89
Batu Caves
Malaysia March 2014
Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice
TNFα MCP1
Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89