Orexin-A对肥胖抵抗大鼠和高脂饮食诱导肥胖大鼠摄食和自由活动的影响

Effects of orexin-A on food intake and spontaneous physical activity in obesity-resistant rats and high-fat diet-induced obese rats

目的:探讨肥胖抵抗(OR)大鼠、高脂饮食诱导肥胖(DIO)大鼠及正常SD大鼠的摄食量和自由活动量的差异及食欲肽(orexin-A)在其中的作用。方法:分别于OR、DIO和SD大鼠下丘脑头端外侧区(r LHa)埋置套管,经套管注射不同剂量(0、31.25、62.5、125和250 pmol)的orexin-A,观察大鼠2 h内摄食量和自由活动情况;采用real-time PCR检测下丘脑和r LHa prepro-orexin、orexin-A受体(OX1R)和orexin-B受体(OX2R)的mRNA表达;采用放射免疫分析法检测下丘脑和r LHa OX1R和OX2R的蛋白含量。结果:r LHa微量注射orexin-A可显著增加OR、DIO和SD大鼠的摄食量(P<0.05);r LHa微量注射orexin-A后,OR和SD大鼠的自由活动量比DIO大鼠显著增高(P<0.05)。OR大鼠r LHA OX1R和OX2R的mRNA及蛋白表达均明显高于DIO和SD大鼠(P<0.05)。结论:下丘脑orexin-A参与肥胖和正常大鼠能量代谢调控,其中对OR大鼠的调控效应最佳。

AIM： To investigate the differences of food intake and spontaneous physical activity（ SPA） among obesity-resistant（ OR） rats,diet-induced obese（ DIO） rats and normal Sprague-Dawley（ SD） rats and the role of orexinA in these processes. METHODS： The rostral lateral hypothalamic area（ r LHa） catheter was implanted into the OIO,OR,and SD rats. Orexin A at doses of 0,31. 25,62. 5,125 and 250 pmol was injected through the catheter. The SPA and food intake were measured and recorded for 2 h after injection. The mRNA expression of prepro-orexin,orexin-A receptor（ OX1R） and orexin-B receptor（ OX2R） in the r LHa and hypothalamus of OR,DIO and SD rats was detected by real-time PCR. The protein expression of OX1 R and OX2 R in the hypothalamus and r LHa of the rats was measured by radioimmunoassay. RESULTS： A small-dose injection of orexin-A into r LHa significantly increased the food intake in all the rats. Orexin A-induced SPA had significant differences,showing that the OR and SD rats had the higher motion than the DIO rats. The mRNA and protein levels of OX1 R and OX2 R in the r LHa of OR rats were significantly higher than those in DIO and SD rats. CONCLUSION： Hypothalamic orexin-A participates in the regulation of energy metabolism in obese and normal rats,in which the regulatory effect on OR rats is the best.