高脂肪膳食对大鼠增食欲素及瘦素系统的影响

The Impact of the High-Fat Diet on the Orexin and the Leptin System in the Rats

目的研究高脂肪膳食诱导的胰岛素抵抗(IR)大鼠下丘脑及脂肪组织中增食欲素和瘦素系统的变化,分析其可能的调控因素。方法IR大鼠模型采用高脂肪膳食诱导并经钳夹技术证实;应用RT-PCR技术检测增食欲素及其受体(OX1R、OX2R)和瘦素受体(LR)以及脂肪组织中瘦素基因mRNA的表达;采用生化比色法测定血清游离脂肪酸(FFA)、放射免疫法测定血清肿瘤坏死因子α(TNF-α)。结果钳夹技术中葡萄糖输注率明显低于对照组;高脂肪膳食诱导的IR大鼠下丘脑中前增食欲素原mRNA的表达较对照组减少约80%(P<0.01);OX1R、OX2R分别增加3.4及3.2倍(P<0.01);瘦素mRNA增加约8倍(P<0.01);LR减少78%;血清FFA和TNF-α均明显高于对照组(P<0.01)。结论高脂肪膳食可诱导大鼠体内IR,并导致增食欲素和瘦素系统平衡状态的破坏;增食欲素和瘦素是机体能量平衡调节网络中的一对重要物质,两者相互作用共同维持机体能量代谢的稳定。血清FFA和TNF-α均可能参与该系统的调控,合理膳食在这一调控中至关重要。

Objective To investigate how high-fat diet affects the changes of orexin and leptin in hypothalamus and fat and analyze the factors regulating this system.Methods The rat model with insulin resistance(IR)induced by high-fat diet was established and confirmed by euglycemic clamp.We examined the mRNA level of orexin,orexin receptor(OX 1 R,OX 2 R)and leptin by reverse transcription-polymerase chain reac-tion.Free fatty acid(FFA)and tumor necrosis factor-α(TNF-α)were measured by biochemical chromato-metry and radioimmunoassay in our study.Results The glucose infusion rate(GIR 60-120 )was much lower com-pared with control group by euglycaemic clamp( P< 0.01).The prepro-orexin mRNA level in hypotha-lamus significantly decreased80%and the leptin in fat increased eight fold in high-fat diet fed rats( P< 0.01),whereas OX 1 R and OX 2 R significantly increased3.4and3.2times,respectively( P< 0.01).FFA and TNF-αincreased concomitantly compared with those of the control group( P< 0.01).Conclusion The status of IR and the unbalance between the orexin and the leptin systems in the rats may be induced by high-fat diet.Orexin and leptin are necessary to maintain the stability of energy metabolism in body,whereas FFA and TNF-αmay be involved in these system.