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Adipose Tissue, Inflammation, and Atherosclerosis
Harald ManggeDepartment of Laboratory Medicine
Medical University of Graz, Austria
BackgroundObesity a global epidemic
The rate of obesity in China has increased by
97% in 10 years, according to a
government report.
Also in
Asia
Obesity Sequels
MI Stroke
HypertensionFatty Liver
postoperative complications
e.g.Sepsis
Type IIDiabetes
Athero-sclerosis
ArthrosisReflux, Infertility
Congenital Defects
Overweight/Obesity
CancerGut, Prostate,
Breast, Renal, LiverEsophagusMelanoma
inflammation
?Cirrhosis, HCC
1975: 1,4 pro 100.000 2006: 3,9 pro 100.000
AtherosclerosisA major burden of obesity
Early beginning
increased IMT
Endstage
Lifelong disease
„Lifestyle“
„fatty streaks“
Chronic immune mediated inflammation
Stroke
0 10 20 30 40 50 60 70 yrs
Clinical endpoints
Chronic vascular inflammation
Immune system
Adipokines SAT Distribution
Obesity
Obesity and AtherosclerosisA complex interaction
Oreopoulos, A. et al. Eur Heart J 2009 30:2584-2592; doi:10.1093/eurheartj/ehp288
The “Obesity Paradox“
BMI < 18.5
BMI = 18.5-24.9
Irrespective of treatment strategy, obese have lower mortality compared to lean patients
Kaplan-Meier survival in patients with established coronary artery disease (CAD)
Ris
k o
f m
ort
alit
y (%
)
Body-Mass-Index
0
50
100
150
200
250
300
I II III
15 18,5 25 30 35 40
Obesity
Despite “Obesity Paradox“Obesity is life-threatening
HypertensionFatty Liver
Type IIDiabetes
Athero-sclerosis
SepsisICU,
Surgery
Cancer
Inflammation
?
• Better outcome in cases of CAD andincreased Mortality in Obesity – a contradiction?
• Answers may be given by the complex function of the adipose tissue.
Lean Obese
Adipose tissueInflammed in obesity
Inflammation
modified fromTilg H., Moschen A.:
Nature Review Immunology, 6:772-83, 2006
lean obese
Proinflammatoryadipokine-cytokine“cocktail“
-++
+++ CCL2 = MCP1
++
IL-6, a principal offender
The Adipose TissueAn Immune / Endocrine Organ
Endocrine activities of adipocytes
adipocyte
Leptin*Eating habits
Resistin, Visfatin
Typ II Diabetes
TNF-aInflammation
IL-6Inflammation
Adiponectin*Vasoprotection
MCP-1(CCL2)Inflammation,
Monocytes
Plasminogen activatorinhibitor (PAI-1)
Clotting
AngiotensinogenBlood pressure
antiinflammatory
proinflammatory
proinflammatory
proinflammatory
proinflammatory
*most abundant adipokines
AdiponectinThree subfractions
High Molecular Weight (HMW)Adiponectin oligomer
Medium Molecular Weight (MMW) Adiponectin hexamer
Low Molecular Weight (LMW)Adiponectin trimer
globular domain
collagenous domain
Oligomerisation
Source
atheroprotective
Monocyte adherence
inflammation
AdiponectinEffects on monocyte adherence
monocytesCXC3CR1hiCCR2−
Ly6ClowCD14lowCD16+
MCP, M-CSF CD40L
TNFa, IL-1, TGFß, MMPs, PDGF, IGF
oxLDL
cell injury byoxLDL, diabetes, infection,
smoking, oxidative stress etc.
Th1-cellsIFNg TNF
TGFß IL-17
monocytesCXC3CR1lowCCR2+
Ly6ChiCD14+CD16−
TNFa, IL-1, TGFß, MMPs, PDGF, IGF-1, MCP-1
Influence of cytokine polymorphisms
+/- +/-
smooth muscle cellsHLA-DR CD40L
AG-presentation proliferation
T-cellsTh1 / Th2
IL-12 IL-18 IL-10
plateletsRANTES
Altered immune reactivity
endothelial cellsICAM, VCAM CCR2, CD40LIL-8, MCP-1
Fractalkin/CX3CR1 PDGF, Selectins
+
+
+
Initiation
Perpetuation
IL-4 ?
?
IL-10?
Local aggravation of arteritis
Acceleratedlesion formation
Complicated lesion
Normal artery Arteritis
RegressionFatty streak
Vicious circle ofinflammation, lipiddeposition, and furtherinflammation
FractalkinRANTESGM-CSFM-CSF
RRrTT
CRP
+
+
PPARsNeopterin
inhibition byß-blockers e.g.
carvedilol, nebivolol
Inhibition byadiponectin
Immmune activation in early and advanced Atherosclerosis
Mangge et al. Clin Chem Lab Med. 42:467-74, 2004 Mangge, Almer et al. Current Medicinal Chemistry, 17:4511-20. 2010
Visceral adipose tissue (VAT)Center of the immune-mediated inflammation
Libby et al Circulation Journal 74:213-220, 2010
LFLow fat diet
HFHigh fat diet
LF HF
Abbr.: CD11c, F4/80, macrophage-, CD3, CD4/8 Tcell-,B220, B-cell-markers.
Balkau et al. Circulation. 2007 October; 116(17): 1942–1951.
Visceral adipose tissue (VAT)Major responsible for CVD (also in lean people)
CVD (cardiovascular disease)Diabetes
CVD (cardiovascular disease)Diabetes
CVD CVD
Obesity research in Graz
STYJOBS / EDECTA Cohort
http://www.meduni-graz.at/styjobs/http://clinicaltrials.gov/ct2/show/NCT00482924
EDECTASTYJOBS
DatabaseBiobank
0 5 10 15 20 25 30 35 40 55 yrs
preclinical Diagnosis (Theragnosis)new individual Risk profiles, Genetics
Early Intervention (nutrition?)
STYrian Juvenile OBesity Study
Public Health
SystemsBiology
LifestyleAging
IT Net-working
Atherosclerosis
PredictionPersonalisation
PreventionLipometry Adipokines Inflammation
Craving Brown / White Adipose Tissue
A body mass index spectrum from 10 to 50 kg/m2from anorexia to morbid adiposity
Early Detection of Atherosclerosis
Lipometry(SAT-TOP)
Complex Database(>200 variables / proband)
Prospective end size n=1600
Bioresource
Biomarkers,Adipokines
Lipids, oxLDLInsulin, conLab
STYJOBS / EDECTAA large set of clinical, anthropometric, laboratory data
Carotissono-graphy (IMT)
0 10 20 30 40 50 60 70 80 years
Complex anthropometry: SAT-Distribution by lipometry
Lipometry
SAT thickness by infrared methodPatent EP2091415
STYJOBS / EDECTAFocus of research I
AdipokinesLow grade inflammation, atherosclerosis, metabolic syndrom, fatty liver, oxStress, craving
adipocyte
Leptin*Eating habits
Resistin, Visfatin
Typ II Diabetes
TNF-aInflammation
IL-6Inflammation
Adiponectin*Vasoprotection
MCP-1(CCL2)Inflammation,
Monocytes
Plasminogen activatorinhibitor (PAI-1)
Clotting
AngiotensinogenBlood pressure
STYJOBS / EDECTAFocus of research II
Wissenschaft und Forschung
Zukunftsfonds
Recent Data
STYJOBS / EDECTA
STYJOBS / EDECTAResults – age range overview, sets of variables
Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity 2008, 2010 PMID: 18846045
Variables Clinical/Anthropometric/Carotis-sono (82)
Laboratory/Biomarkers/Adipokines (100)Glucose metabolism, liver, kidney function, lipids, oxidative/nitrosative stress, adipokines, orphane vascular markers, clotting
Genetic/mitochondrial function/miscellaneous (100)
PatientsN=890
IntendedN=1500
STYJOBS / EDECTAResults, vascular/inflammatory/metabolic markers
Adiponectin
US-CRPCarotis IMT
syst Bloodpressure HOMA-index
Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity 2008, 2010 PMID: 18846045
R=0.25P<0.01
R=0.34P<0.01
R=0.29P<0.01
R=0.58P<0.01
R=0.48P<0.01
(-) (+)
Interleukin-6R=0.33P<0.01
BMI(-) (+)
STYJOBS / ResultsUltrasonography of CCA Intima Media Thickness (IMT)*
p < 0.001
,03
,04
,05
,06
,07
,08
,09
,1
,11
A. c
aro
tis
com
mu
nis
IMT
cm
Overweight/obese (n=370)Controls (n=153)
13y
IMT
Mangge et al Exp Clin Endocrinol Diabetes. 2004.PMID: 1523902Mangge et al Atherosclerosis 2008, PMID: 18656877 Mangge et al Obesity 2009, PMID: 18846045
STYJOBS, age below 18 years, n=523
STYJOBS/ResultsIMTUS-CRP (Inflammation)
p <0.001
weak correlation
R=0.18
STYJOBS, age < 18 years
STYJOBS / ResultsIMT versus waist
Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity Research 2008, PMID: 18846045
Excellent correlation
Waist circumference vs Carotis IMT
R=0.5
STYJOBSage < 18 years
Visceral adipose tissue (VAT)Center of the immune-mediated inflammation
Libby et al Circulation Journal 74:213-220, 2010
LFLow fat diet
HFHigh fat diet
LF HF
Abbr.: CD11c, F4/80, macrophage-, CD3, CD4/8 Tcell-,B220, B-cell-markers.
STYJOBS / ResultsIntima media thickness versus transaminases
Mangge et al Exp Clin Endocrinol Diabetes. 2004.PMID: 1523902Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity 2008, PMID: 18846045
STYJOBS, age < 20 years, n=523
***
r=0.37p<0.01
STYJOBS / EDECTA
Lipometry
SAT thickness by infrared methodPatent EP2091415
STYJOBS / ResultsIMT versus Anthropometry
Multiple Regression includingBMI, %bodyfat, waist, hip, waist to height ratio, lipo measure points 1-15, Adiponectin subfractions
Multiple Regression includingBMI, %bodyfat, waist, hip, waist to height ratio, lipo measure points 1-15
Preis SR, Massaro JM, Hoffmann U, D'Agostino RB
Sr, Levy D, Robins SJ, Meigs JB, Vasan RS, O'Donnell CJ, Fox CS.
Neck circumference as a novel measure of cardiometabolic risk: the Framingham Heart study.
Neck circumference is associated with CVD risk factors even after adjustment for VAT and BMI. These findings suggest that upper-body sc fat may be a unique, pathogenic fat depot.
J Clin Endocrinol Metab. 2010 Aug;95(8):3701-10. Epub 2010 May 19.
STYJOBS / ResultsHMW, MMW, LMW / total adiponectin ratios
HMW / total adiponectin
MMW / total adiponectin
LMW / total adiponectin
Mangge et al. Preatherosclerosis and adiponectin subfractions in obese adolescents. Obesity, 2008, PMID:18846045Nuchal thickness of subcutaneous adipose tissue is tightly associated
with an increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis, 2009, PMID:18656877
High Molecular Weight (HMW)
adiponectin oligomer
Medium Molecular Weight(MMW)
adiponectin hexamer
Low Molecular Weight (LMW)
adiponectin trimer
Oligomerisation disturbed ?
STYJOBS / ResultsAdiponectin
HDL-cholesterol is
HMW Adiponectin decrease is closely associated with
increased carotis IMT
Mangge et al. Preatherosclerosis and adiponectin subfractions in obese adolescents. Obesity, 2008, PMID:18846045Nuchal thickness of subcutaneous adipose tissue is tightly associated
with an increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis, 2009, PMID:18656877
Results of a multiple regression
HDL-cholesterol is
LMW Adiponectin increaseis closely associated with
nuchal fat thickness
Results of a multiple regression
Szmitko et alAm J Physiol Heart Circ Physiol 292: 1655-1663, 2007.
Adiponectin HMW fraction most effective against AS
STYJOBS / ResultsOxidative stress, oxidative LDL
HDL-cholesterol is HDL cholesterol is the best predictor for lipid peroxidation irrespective of age, gender, and
other biomarkers
Mangge et al. High density lipoprotein cholesterol level is a robust predictor of lipid peroxidationirrespective of gender, age, obesity, and inflammatory or metabolic biomarkers
ClinicaChimActa, 2011, in press
Results of the multiple regression
STYJOBS / EDECTAResults - Cardiovascular risk pattern
with emphasis on BMI, Age, Gender
Age(-) (+)
Carotis IMT Systolic BP Diastolic BP
STYJOBS / EDECTAResults - Hepatic risk patternwith emphasis on BMI, Age, Gender
Age(-) (+)
Cholinesterase ALT/GPT gammaGT
ALT/GPT cut offFemale adult <40 U/L, <15years < 25 Male adult <30, <15years < 25
STYJOBS / EDECTA
Results
Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity 2009, PMID: 18846045Mangge et al Current Med Chem, 2010 PMID:21062254
Consider earlydevelopment of gender
related risk profiles!
STYJOBS / EDECTA - ResultsSummary
HMW adiponectin is decreased in the early phase of vascular abnormalities in obesity.
As the LMW subfraction is increased, and the HMW subfraction decreased, the oligomerisation from LMW to HMW adiponectin may be disturbed.
Trunk weighted obesity is associated with very low HMW adiponectin, and stronger increased carotis IMT.
HDL cholesterol decrease is the best predictor for lipid peroxidation.
Mangge et al Atherosclerosis 2009, PMID: 18656877 Mangge et al Obesity Research 2008, PMID: 18846045
General conclusion
Obesity is a chronic inflammatory disease.
Irrespective of sex, age and gender, the inflammatory activation associated with abdominal fat accumulation is crucial for obesity related sequels like atherosclerosis.
Adipokines are centrally involved in the chronic inflammation of obesity. The balancebetween the most abundant adipokines , adiponectin and leptin may be crucial for the clinical course of atherosclerosis.
The “obesity paradox” may be explained by “protective” antiinflammatory qualities of the adipose tissue. However, abdominal (trunk) obesity abrogates the protective effects.
Therapeutic modification of chronic low grade inflammation with reference to the individual SAT distribution may become an important challenge for the future.
STYJOBS / ResultsConclusion
Our data show that already the early phase of obesity is associated with chronic
inflammation, preatherosclerosis, and an essentially altered adipokine synthesis.
SAT- distribution (visceral, nuchal) is a crucial risk factor.
Pilz S, Mangge H et al. J of Clin Endocrinology and Metabolism, PMID: 15928248, 2005Moeller R, Mangge H et al. Obesity, PMID: 17495209, 2007
Gruber H, Mangge H et al. Int J of Obesity PMID: 18656877, 2008Mangge et al. Atherosclerosis, PMID: 18656877, 2009
Mangge et al. Obesity, PMID: 18846045, 2009Wallner, Mangge et al, PMID:20168310, 2010
Mangge et al Current Med Chem, PMID:21062254, 2010Fritsch, Mangge et al Atherosclerosis, PMID:21334626, 2011
Mangge, Renner et al, PMID:21318054, 2011Mangge et al ClinChimActa, 2011, in press
http://www.meduni-graz.at/styjobs/http://clinicaltrials.gov/ct2/show/NCT00482924
Thank you for the attention!
Libby et al Circulation Journal 74:213-220, 2010
JUPITER-Trial
SubjectsNo history of CAD
LDL-cholesterol <3.4mmol/L
CRP > 19.0nmol/L
Random treatment
Rosuvastatin 20mg daily or
Placebo
STYJOBS / EDECTALeptin
Leptin R=0.68P<0.01N=804
STYJOBS / EDECTAUric acid, HDL-cholesterol…vs BMI
BMI
Uric acid HDL-cholesterol ox-LDL
BMI mother BMI fatherLDL-cholesterol
Mangge et al Atherosclerosis 2009, PMID: 18656877
Mangge et al Obesity 2008, PMID: 18846045
R=0.5 R=0.28 R=0.19
n.s. R=0.38 R=0.29
Juvenile ObesityReduces life expectancy
Franks PW et al. Childhood Obesity, Other Cardiovascular Risk Factors, and Premature
Death. N Engl J Med. 11; 362:485-493, 2010
Childhood obesity is associated with premature death in adulthood
Followed,
obese children
(american
indians),
not suffering
from diabetes.
Early ObesityFactors associated with premature death from endogenous causes
Childhood hypertension was strongly associated with the rate of death from endogenous causes
in early adulthood (incidence-rate ratio, 1.57; 95% CI, 1.10 to 2.24).
No significant associations were observed between death rates and childhood cholesterol levels*.
*Franks PW et al. Childhood Obesity, Other Cardiovascular Risk Factors, and Premature
Death. N Engl J Med. 11; 362:485-493, 2010
STYJOBS age<20y
R = 0.5
P<0.01
R =-0.5
P<0.01
n.s.
Future activities
Epigenetics, miRNAs and white/brown AT, Fatty Liver Disease ↔ Nutrition, Modulation of Craving
internet
http://clinicaltrials.gov/ct2/show/NCT00482924
http://www.meduni -graz.at/styjobsFrom 1 st
decade
From 2 nd
decade
From 3 rd
decade
Tackling the early burden in obesity
From 1 st
decade
From 2 nd
decade
From 3 rd
decade
Tackling the early burden in obesity
STYJOBS / EDECTAWhere we are at the moment870 probands recruited, 1500 intended
Human evolution – the shape of things to come?
Nuchal fat, White/Brown AT, Vascular Risk, Adipokines Hippocampus, Craving, Insulin, SAT distribution
STYJOBS / EDECTAScope of recent publications
Stelzer, Mangge et al. Clinical Chemistry, submitted 2011 Focus Clotting, IL-6, InflammationRaggam, Prüller, Mangge et al. Obesity, submitted 2011 Focus ClottingZelzer, Mangge et al. Clinica Chimica Acta, in press, 2011 Focus Biomarkers (oxLDL) Mangge, Almer, Renner et al. Journal of Obesity, PMID: 21318054, 2011 Focus Genetics (FTO Gen), SAT-TopographyMangge, Fuchs et al. Journal of Obesity, PMID: 21274279 2011 Focus Biomarkers (Neopterin)Arnold, Mangge, Strobl et al. Pediatric Research, PMID: 21135756, 2011 Focus Biomarkers (Clusterin)Mangge, Fuchs et al. Current Medicinal Chemistry, PMID: 21062254, 2010Focus Atherosclerosis (Inflammation, AT)Fritsch, Mangge et al. Atherosclerosis PMID: 20619835, 2010 Focus Clotting (ETP, procoagulant PPLs)Wallner-Liebmann, Mangge et al. Obesity PMID: 20168310, 2010 Focus Craving (Insulin, Hippocampus)Mangge et al. Atherosclerosis, PMID: 18656877, 2009 Focus Biomarkers (Adiponectin)Mangge et al. Obesity, PMID: 18846045, 2009 Focus Adiponectin (SAT Topography)Gruber H, Mangge H et al. Int J of Obesity PMID: 18656877, 2008 Focus Atherosclerosis (Oxidative“Stress”)Mangge, Almer et al. Diabetes Care PMID: 18375422, 2008 Focus Insulin resistance (Metabolism)Truschnig, Mangge et al. Exp and Clin Endocrinol & Diabetes, PMID: 18072008, 2008 Focus Atherosclerosis (Food Allergy)Moeller, Mangge et al. Obesity, PMID: 17495209, 2007 Focus Atherosclerosis (SAT Topography)Pilz, Mangge et al. J of Clin Endocrinology and Metabolism, PMID: 15928248, 2005 Focus Atherosclerosis (Adiponectin)Mangge et al. Exp and Clin Endocrinology & Diabetes, PMID: 15239023, 2004 Focus Atherosclerosis (Inflammation)
STYJOBS / EDECTAFocus interdisciplinarity
PartnersMedical-, Karl Franzens-, Technical-Universities of Graz
Gunter Almer, Verena Biedermann, Andreas Meinitzer, Florian Freytag, Renate Horejsi, Reinhard Möller, Clemens Diwoki, Wolfgang Schnedl, Kerstin Hingerl, Karl Koschutnig, Gernot Reishofer, Renate Kruschitz, Barbara Blaschitz, Matthias Saba-Lepek, Marcel Scheideler, Robert Gasser,
Elisabeth Kraigher-Krainer, Martie Truschnig-Wilders, Sieglinde Zelzer, BioNanoNet, Peter Opriessnig, Ruth Prassl, Paul Debagge, Peter Hofmeister, Rudolf Stollberger, Andreas Zimmer, FattyLiverResearch Consortium, Sandra Wallner-Liebmann, Caroline Lackner, Johannes
Haybäck, Peter Abuja, Rudolf Stauber, Rottraud Ille, Harald Mangge
ExternalParacelsus Privatuniversität Salzburg
Walter Sperl, Daniel Weghuber, Friedrich Hoppichler, intended cooperation with the
University of MunichReinhard Halle, Sportsmedicine
Boston University School of Medicine, Framingham Vasan S. Ramachandran
Wissenschaft und ForschungZukunftsfonds
STYJOBS / ResultsInterleukin-6
Mangge et al. Chronic inflammation in obesity:
Fibrinogen is an independent predictor for interleukin-6 in juveniles and adults ClinicalChemistry, 2011, submitted
Fibrinogen is the best predictor for Interleukin-6 irrespective of age, gender, and other biomarkers
Results of the multiple regression
Carotid intima-media thickening indicates a higher vascular risk across a wide age
range: prospective data from the Carotid Atherosclerosis Progression Study (CAPS).
Lorenz et al. Stroke, 2006
"Its predicitive value is as high in younger subjects as in older subjects"
IMT determination of CCAsResults of a recent study
STYJOBSResults
Metabolic Profiles
STYJOBS/ResultsBlood pressure
HO
MA
in
de
x20
15
10
5
0
p <0.0001
obesecontrol
sys
toli
c b
loo
d p
res
su
re (
mm
Hg
)
180
160
140
120
100
80
60
p <0.01
r = 0.5 p < 0.001
Mangge et al Atherosclerosis 2008, PMID: 18656877
Mangge et al Obesity Research 2008, in press
STYJOBSResults
Glucose metabolism
STYJOBS/ResultsGlucose metabolism
obesecontrols
HO
MA
in
de
x20
15
10
5
0
p <0.0001HOMA-Index =
FI x FGlu : 22,5
FI = fasting insulin
FGlu = fasting
glucoseGlucose mmol/L
Insulin uE/ml
HOMA IR =
homeostatic model
assessment - insulin
resistanceMangge et al,
Int J of Obesity,
2006, in press
STYJOBS/ResultsDiabetes
obesecontrols
HO
MA
in
de
x20
15
10
5
0
p <0.0001
HOMA-Index =
FI x FGlu : 22,5
FI = fasting insulin
FGlu = fasting
glucoseGlucose mmol/L
Insulin uE/ml
HOMA IR =
homeostatic model
assessment - insulin
resistance
Mangge et al
Atherosclerosis
2008, PMID:
18656877
Mangge et al
Obesity Research
2008, in press
STYJOBSResults
Liver function
STYJOBS/ResultsLiver enzymes I
p = 0.03 p < 0.0001
n.s. p < 0.0001
r = 0.35
STYJOBS/ResultsLiver enzymes II
p < 0.0001 p < 0.0001
p < 0.0001
r = 0.2
p < 0.0001
r = 0.24
STYJOBSResults
Lipids, Uric Acid,
Oxidative / Nitrosative “Stress”
STYJOBS/ResultsHDL-cholesterol, oxLDL
20
30
40
50
60
70
80
90
HD
L-C
ho
leste
rin
mg
/dl
controls obese
***
Mangge H, Pilz S. Journal of Clinical Endocrinology and Metabolism 2005
STYJOBS / ResultsLipid profile, and uric acid
p < 0.001 p < 0.0001 p < 0.001 p < 0.0001
Fatty acids Triglycerides VLDL-Cholesterol Uric acid
STYJOBS / ResultsTotal NO (NOX), oxLDL
Gruber H, Mangge H et al. International J Obesity, 32(5): 826-31, 2008 PMID: 18197180,
p < 0.001
(MannWithney)
Source, Libby et al Circulation Journal 74:213-220, 2010
MonocytesPrincipal offenders in atherogenesis
Obesity in EuropeAdults
Adults
BMI > 30 Source: IASO
International Obesity
TaskForce
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
Obesity in EuropeJuveniles
Kids
around 10 years*
> 30%
20 - 29.9%
10 - 19.9%
no data
Source: IASO
International Obesity TaskForce
modified from
Tilg H., Moschen A.:
Nature Review Immunology, 6:772-83, 2006
AdiponectinReceptors
Antiinflammatory effect
(mainly in liver)
(endothelial,
smooth muscle
cells)
↓ Oxidative stress
↓ Apoptosis
T-Cadherin
Okamoto, Y. et al. Circ Res 2008;102:218-225
IP-10, Mig, and I-TAC are expressed in M, endothelial cells, and
smooth muscle cells in vasculature. They recruit T-lymphocyte
migration, important for the development of atheromata
Adiponectin
Chemokine suppression
Inhibition of of CXCR3 chemokine ligand expression
Adiponectin reduces IP-10, Mig, and I-TAC mRNA levels in human M
Abbrevations
APN, Adiponectin
IP, INFg induced protein
Mig, Monokine induced by gINF
I-Tac, INF-inducible Tcell Alpha chemoattractant
Obesity in EuropeAdults
AdultsBMI > 30
Source: IASO International Obesity
TaskForce
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
Obesity in EuropeJuveniles
Kidsaround 10 years*
> 30%
20 - 29.9%
10 - 19.9%
no data
Source: IASO International Obesity TaskForce