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

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• 作者：J.M. do Carmo^a ; ^{jdocarmo@umc.edu} ; A.A. da Silva^a ; J. Morgan^a ; Y.-X. (Jim) Wang^b ; S. Munusamy^a ; J.E. Hall^a
• 关键词：Obesity ; Energy expenditure ; Epoxide hydrolase inhibition ; Body weight ; Oxygen consumption
• 刊名：Nutrition ; Metabolism and Cardiovascular Diseases
• 出版年：2012
• 期刊代码：233_09394753
• 类别：med
• 出版时间：July, 2012
• 卷：22
• 期：7
• 页码：598-604
• 文件大小：668 K

摘要

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, 200 mg/kg/day by gavage twice daily), and 2) vehicle (0.3 ml per gavage). Food intake, body weight, oxygen consumption (VO₂), carbon dioxide production (VCO₂), respiratory quotient (RQ), and motor activity were measured weekly for more 5 weeks. HFD increased body weight (37 卤 1 vs. 26 卤 1 g), and plasma of glucose (316 卤 8 vs. 188 卤 27 mg/dl), insulin (62.1 卤 8.1 vs. 15.5 卤 5.0 渭U/ml), and leptin levels (39.4 卤 3.6 vs. 7.5 卤 0.1 ng/ml) while reducing VO₂, VCO₂ and motor activity. s-EH inhibition for 5 weeks decreased caloric intake by 鈭?2%and increased VO₂ by 鈭?7%(42.8 卤 1.4 vs. 50.2 卤 1.5 ml/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 鈭?0%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.