Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505, United States.
Nutr Metab Cardiovasc Dis. 2012 Jul;22(7):598-604. doi: 10.1016/j.numecd.2010.10.017. Epub 2010 Dec 28.
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.
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.
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.
本研究评估了在喂食高脂肪高果糖饮食（HFD）10 周的小鼠中，对可溶型环氧水解酶（s-EH）抑制（一种花生四烯酸代谢的必需酶）的反应，以观察其对食物摄入、体重和代谢参数的影响。
在 HFD 喂养 5 周后，将小鼠分为两组：1）s-EH 抑制剂（AR9281，每天两次通过灌胃 200mg/kg），和 2）载体（每次灌胃 0.3ml）。在接下来的 5 周内每周测量食物摄入、体重、耗氧量（VO₂）、二氧化碳生成量（VCO₂）、呼吸商（RQ）和运动活动。HFD 增加了体重（37±1 比 26±1g），并增加了血浆葡萄糖（316±8 比 188±27mg/dl）、胰岛素（62.1±8.1 比 15.5±5.0μU/ml）和瘦素水平（39.4±3.6 比 7.5±0.1ng/ml），同时降低了 VO₂、VCO₂和运动活动。5 周的 s-EH 抑制减少了约 32%的热量摄入，并增加了约 17%的 VO₂（42.8±1.4 比 50.2±1.5ml/kg/min），导致显著的体重减轻。s-EHi 的抑制还导致血浆瘦素水平和内脏脂肪含量的显著降低。与载体处理相比，s-EH 抑制还使棕色脂肪组织中的解偶联蛋白 1（UCP1）含量增加了约 50%。
这些结果表明，用 AR9281 抑制 s-EH 通过减少食欲和增加代谢率来促进体重减轻，而 UCP1 含量的增加可能有助于增加能量消耗。
