下丘脑Orexin对肥胖大鼠能量代谢的影响

The Effects of Hypothalamic Administration of Orexin on Metabolism in Diet-induced Obese Rats

目的:探讨下丘脑注射OXR-1选择性受体拮抗剂ACT-335827对肥胖大鼠代谢的效果。方法:通过高脂饮食建立肥胖大鼠模型,采用CODA 8通道高通量非侵入性血压系统(EMKA)测量血压;所有脂类都使用商品酶试剂盒和TOSHIBA-40FR全自动分析仪测量;空腹血糖采用葡萄糖氧化酶法;空腹胰岛素采用放射免疫法测定。肥胖大鼠出现代谢紊乱后,给予ACT-335827处理,检测大鼠体重、血压、脂肪、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、游离脂肪酸(NEFA)、瘦素、空腹血糖及空腹胰岛素等的变化。结果:与普通饮食组相比,经过10周高脂饮食,高脂饮食组大鼠体重显著升高(P<0.05),给予ACT-335827处理后,普通大鼠的体重、血压、脂肪含量、脂代谢等均无明显变化;与高脂饮食和高脂饮食加生理盐水处理组大鼠比较,高脂饮食加ACT-335827处理组肥胖大鼠的体重显著下降(P<0.05),腹部和附睾脂肪含量下降(P<0.05),低密度脂蛋白、甘油三酯、总胆固醇、瘦素水平下降(P<0.05),空腹血糖及空腹胰岛素也显著降低(P<0.05),但血压、肠系膜脂肪和肩胛棕色脂肪、高密度脂蛋白和NEFA无明显变化(P<0.05)。结论:ACT-335827对肥胖大鼠的代谢紊乱具有改善作用,对肥胖大鼠有一定的减肥作用。

Objective： To investigate the effects of hypothalamic administration of OXR-1 selective antagonist ACT-335827 on the metabolism of high-fat diet induced obese rats. Methods： Obese rat model was established by high fat diet feeding. Blood pressure was indirectly measured by blood volume pressure recording （VPR） from the tail using the CODA 8-channel high throughput non-inva- sive blood pressure system （EMKA）. All plasma lipids were measured using commercial enzyme assay kits and a TOSHIBA-40FR fully automated analyzer. Fasting blood glucose was measured using glucose oxidase kit. Fasting insulin was measured by radioimmunoassay. When obese rats displayed metabolic disorders, ACT-335827 was given for the treatment. The changes in body weight, blood pressure, fat, plasma triglycerides, total cholesterol, high density lipoprotein, low density lipoprotein, non-esterified fatty acid （NEFA）, leptin, fast- ing blood glucose and fasting insulin were measured. Results： Compared with standard chow groups, the body weight of rats in high-fat diet groups were significantly increased after 10 weeks of high fat diet feeding （P〈0.05）. After ACT-335827 treatment, the body weight, blood pressure, fat content and lipid metabolism of rats in standard chow groups did not change significantly （P〉0.05）; compared with high-fat diet group and high-fat diet with normal saline treatment group, the body weight of high fat diet feeding rats with ACT-335827 treatment was significantly decreased （P〈0.05）. Similarly, the abdominal and epididymal fat content were decreased （P〈0.05）; low-density lipoprotein, triglycerides, total cholesterol and leptin levels were decreased （P〈0.05）; fasting glucose and fasting insulin were significantly reduced （P〈0.05） in high-fat diet feeding rats with ACT-335827 treatment. However, blood pressure, mesenteric fat and scapular brown fat, high-density lipoprotein and NEFA of these rats were not remarkably changed （P〈0.05）. Conclusions： ACT-335827 could improve the metabolic disorders in high fat induced obese rats, and ACT-335827 may play a role in weight loss in high fat induced obese rats.