Inhibition of soluble epoxide hydrolase reduces food intake and increases metabolic rate in obese mice.

Abstract

BACKGROUND AND AIMS:

This study evaluated the responses to soluble epoxide hydrolase (s-EH) inhibition, an essential enzyme in the metabolism of arachidonic acid, on food intake, body weight and metabolic parameters in mice fed a high fat-high fructose diet (HFD) for 10 weeks.

METHODS AND RESULTS:

After 5 weeks of HFD, mice were divided into two groups: 1) s-EH inhibitor (AR9281, 200mg/kg/day by gavage twice daily), and 2) vehicle (0.3ml per gavage). Food intake, body weight, oxygen consumption (VO(2)), carbon dioxide production (VCO(2)), respiratory quotient (RQ), and motor activity were measured weekly for more 5 weeks. HFD increased body weight (37±1 vs. 26±1g), and plasma of glucose (316±8 vs. 188±27mg/dl), insulin (62.1±8.1 vs. 15.5±5.0μU/ml), and leptin levels (39.4±3.6 vs. 7.5±0.1ng/ml) while reducing VO(2), VCO(2) and motor activity. s-EH inhibition for 5 weeks decreased caloric intake by ~32% and increased VO(2) by ~17% (42.8±1.4 vs. 50.2±1.5ml/kg/min) leading to significant weight loss. Inhibition of s-EHi also caused significant reductions in plasma leptin levels and visceral fat content. Uncoupling protein 1 (UCP1) content in brown adipose tissue was also elevated by ~50% during s-EH inhibition compared to vehicle treatment.

CONCLUSION:

These results suggest that s-EH inhibition with AR9281 promotes weight loss by reducing appetite and increasing metabolic rate, and that increased UCP1 content may contribute to the increase in energy expenditure.

• Authors: J M do Carmo, A A da Silva, J Morgan, Y-X Jim Wang, S Munusamy, J E Hall
• Journal: Nutrition, metabolism, and cardiovascular diseases : NMCD (Nutr Metab Cardiovasc Dis) Vol. 22 Issue 7 Pg. 598-604 (Jul 2012) ISSN: 1590-3729 [Electronic] Netherlands
• PMID: 21190818 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Blood Glucose
• Dietary Fats
• Hormones
• Insulin
• Ion Channels
• Leptin
• Mitochondrial Proteins
• Ucp1 protein, mouse
• Uncoupling Protein 1
• Uncoupling Protein 3
• Arachidonic Acid
• Fructose
• Epoxide Hydrolases

Topics

• Adipose Tissue, Brown (chemistry)
• Animals
• Arachidonic Acid
• Blood Glucose (analysis)
• Body Weight
• Diet
• Dietary Fats (administration & dosage)
• Energy Intake
• Energy Metabolism
• Epoxide Hydrolases (antagonists & inhibitors, metabolism)
• Fructose (administration & dosage)
• Hormones (blood)
• Insulin (blood)
• Ion Channels (analysis, metabolism)
• Leptin (blood)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Mitochondrial Proteins (analysis, metabolism)
• Obesity (metabolism)
• Oxygen Consumption
• Uncoupling Protein 1
• Uncoupling Protein 3