Department of Internal Medicine, University of Texas Southwestern Medical Center, United States.
Physiol Behav. 2011 Apr 18;103(1):10-6. doi: 10.1016/j.physbeh.2011.01.010. Epub 2011 Jan 15.
Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of LF and chow rats but had no effect on HF rats in either the chronic or the acute experiment. Rats chronically pair-fed the HF diet to match the caloric intake of LF rats, and with body weights and adiposity levels comparable to those of LF rats, were also unresponsive to i3vt insulin when returned to ad libitum food whereas rats pair-fed the LF diet had reduced food intake and body weight when administered i3vt insulin. Insulin's inability to reduce food intake in the presence of the high-fat diet was associated with a reduced ability of insulin to activate its signaling cascade, as measured by pAKT. Finally, i3vt administration of insulin increased hypothalamic expression of POMC mRNA in the LF- but not the HF-fed rats. We conclude that consumption of a HF diet leads to central insulin resistance following short exposure to the diet, and as demonstrated by reductions in insulin signaling and insulin-induced hypothalamic expression of POMC mRNA.
血浆胰岛素进入中枢神经系统，在与能量平衡相关的区域与胰岛素受体相互作用，导致食物摄入量和体重减少。在这里，我们证明高脂肪（HF）饮食会损害胰岛素的中枢作用。雄性长耳大仓鼠给予慢性（70 天）或急性（3 天）自由摄取高脂肪、低脂肪（LF）或标准饮食。胰岛素注入第三脑室内（i3vt）可减少 LF 和标准饮食大鼠的食物摄入量和体重，但对慢性或急性实验中的 HF 大鼠均无影响。HF 饮食组的大鼠进行慢性等热量喂养，以匹配 LF 饮食组的热量摄入，并且体重和肥胖程度与 LF 饮食组相当，当恢复自由进食时，对 i3vt 胰岛素也无反应，而 LF 饮食组的大鼠给予 i3vt 胰岛素后，食物摄入量和体重减少。在高脂肪饮食存在的情况下，胰岛素不能减少食物摄入量与胰岛素激活其信号级联的能力降低有关，如 pAKT 所示。最后，i3vt 给予胰岛素可增加 LF 饮食喂养大鼠而不是 HF 饮食喂养大鼠的下丘脑中 POMC mRNA 的表达。我们得出结论，短期暴露于高脂肪饮食会导致中枢胰岛素抵抗，如胰岛素信号降低和胰岛素诱导的 POMC mRNA 在下丘脑中的表达减少所证明的那样。
