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Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

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Page 1: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,
Page 2: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD

Dietary Protein Research Group, Department of Clinical Medicine, University of Bergen

Ola Flesland and Rune G. Madsen

TripleNine, Denmark

Fish proteins from blue whiting may promote health benefits in pets

Page 3: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

59.5% of cats and 55.8% of dogs in the US are classified as overweight or obese,

according to the Association for Pet Obesity Prevention (APOP)

That is approximately 56 million cats and 50 million dogs

Pets are getting fatter and sicker

Page 4: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

• Type 2 diabetes

• Reduced insulin sensitivity

• High blood pressure (hypertension)

• Coronary heart disease

• High cholesterol

• Fatty liver

• Kidney disease

Obesity increases the risk of developing

Page 5: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

• Type 2 diabetes

• Reduced insulin sensitivity

• High blood pressure (hypertension)

• Coronary heart disease

• High cholesterol

• Fatty liver

• Kidney disease

Obesity increases the risk of developing

Page 6: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

In humans, several (but not all!) studies show lower prevalence of obesity and obesity related

comorbidities in populations with high fish intake

Animal studies show beneficial effects of intake of fish (filet), fish oil and fish proteins on

diseases associated with obesity

Prevalence of obesity and comorbidities

Page 7: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Develop obesity around 4 weeks of age

Develop high blood pressure, kidney damage, diabetes and high cholesterol with

increasing degree of obesity

Obese Zucker fa/fa rats

Page 8: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Blood pressure development in Zucker rats

From: Luo 2015

100

110

120

130

140

150

160

170

180

9 10 11 12 13 14

80

90

100

110

120

130

140

9 10 11 12 13 14

Obese Zucker

Lean Zucker

Systolic blood pressure Diastolic blood pressure

Age, weeks Age, weeks

Page 9: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

No anesthesia necessary

Five measurements takes 6 min

Rats rest on a warming plate (37°C)

We measure diastolic and systolic

blood pressure and heart rate

Page 10: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

A small pelagic fish primarily used to produce fish meal for aquaculture feed

Its small size and discoloration limits the market for blue whiting as whole fish or fillet

for human consumption

In 2016, the world’s total catch of blue whiting amounted to 1.19 million tonnes.

Blue whiting consists 19-20% protein and has an average fat content of 5%

Blue whiting (Micromesistius poutassou)

Page 11: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Fish was headed and gutted, added water and heated to 90°C

The cooked material was mechanically dewatered in a double-screw press to produce

stickwater (water-soluble fraction) and presscake (water-unsoluble fraction).

A whole meal was produced by combining the two fractions.

Hydrolysates were produced by enzymatic hydrolysis (alcalase and Protamex) of the whole meal

Blue whiting (Micromesistius poutassou)

Page 12: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Blue whiting (Micromesistius poutassou)

Composition of the experimental diets 1

Contents (g/kg diet) Control diet BWW diet

Casein1 216.00 144.00

Blue Whiting Water-Soluble Fish Protein2

108.30

Cornstarch 511.67 475.50

Sucrose 90.00 90.00

Cellulose 50.00 50.00

Soybean Oil 70.00 70.00

t-Butylhydroquinone 0.015 0.015

Mineral Mix (AIN-93-MX) 35.00 35.00

Vitamin Mix (AIN-93-VX) 10.00 10.00

L-Methionine 1.60 1.60

L-Cystine 3.00 3.00

Choline Bitartrate3 2.50 2.50

Growth and maintenance supplement (#410751) 4

10.00 10.00

1 contains 92.5 % crude protein, 2 contains 61.5 % crude protein, 3 contains 41 % choline, 4 contains vitamin B12 2

(40 mg/kg) and vitamin K1 (25 mg/kg) mixed with sucrose (995 g/kg) and dextrose (5 g/kg). BWW: Blue 3

whiting water-soluble protein 4

Page 13: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Blue whiting stickwater

Page 14: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Blue whiting stickwater

Aim:

To investigate the effects of a diet containing water-soluble protein from blue whiting on

cholesterol metabolism in obese Zucker fa/fa rats

Page 15: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Blue whiting stickwater

Page 16: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Blue whiting stickwater

Page 17: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Blue whiting stickwater

Page 18: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

• Reduce serum cholesterol concentration

• Reduce cholesterol amount in liver

• Mechanism of action: reduce the body’s own cholesterol production

Blue whiting stickwater: conclusions

Page 19: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Aim:

Primary: To compare the effects of diets containing proteins from headed and gutted

blue whiting as whole meal or protein hydrolysates on the development of high blood pressure

in obese Zucker fa/fa rats.

Secondary: To investigate any changes in markers of kidney function, organ damage,

inflammation and oxidative stress, to examine the in vitro ACE and renin inhibiting properties of the blue whiting proteins.

Blue whiting presscake (not published yet)

Page 20: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Background:

Fish proteins have been shown to inhibit angiotensin-converting enzyme (ACE) in vitro

Blue whiting presscake

Page 21: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,
Page 22: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Prevented blood pressure increase by 20% in obese Zucker fa/fa rats

Effects on blood pressure did not correspond with in vitro ACE activity

Kidney function was not affected

No changes in inflammation and antioxidant stress

Blue whiting presscake: conclusions

Page 23: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Aim:

Investigate if proteins from residual material and filet have different effects on

blood pressure development in obese Zucker fa/fa rats

Cod proteins

Page 24: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,
Page 25: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

The mean arterial pressure (MAP) was calculated as (diastolic blood pressure + 1/3 (systolic blood pressure - diastolic blood pressure)). SW-H; stickwater from Havstrand, PC-H; presscake meal from Havstrand, SWPC-H; stickwater + presscake meal from Havstrand, PC-G; presscake meal from Granit, FM-G; fillet meal from Granit.

Page 26: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Figure 3. In vitro inhibition of activities of

angiotensin-converting enzyme (A)

and renin (B). Values are means, with

standard error of mean represented as

vertical bars. Values are shown for two

or three measurements for casein and

cod protein meals. Proteins are

compared using one-way ANOVA with

LSD post hoc test. Bars with different

letters are significantly different (p <

0.05). SW-H; stickwater from Havstrand,

PC-H; presscake meal from Havstrand,

SWPC-H; stickwater + presscake meal

from Havstrand, PC-G; presscake meal

from Granit, FM-G; fillet meal from

Granit.

Page 27: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Presscake meal from cod residual materials with high gut content (PC-H) effectively

prevented the increases in MAP that are normally observed in obese Zucker fa/fa rats,

whereas the other cod meals tested did not influence the blood pressure development in

these rats.

In line with this, PC-H had the strongest effect on in vitro inhibition of ACE and renin

activities of the cod meals tested.

Cod proteins: conclusions

Page 28: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Investigate effects of fish proteins on blood pressure and kidney function in dogs

Prevention vs treatment

Elucidate the mechanism(s) of action

Future perspectives

Page 29: Oddrun Anita Gudbrandsen, PhD, and Aslaug Drotningsvik, PhD€¦ · • High cholesterol • Fatty liver • Kidney disease Obesity increases the risk of developing ... In humans,

Oddrun Anita Gudbrandsen: [email protected]

Ola Flesland: [email protected]

Rune Guldager Madsen: [email protected]

Contact