Department of Mouse Genetics and Metabolism, Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Center of Molecular Medicine, University of Cologne,Cologne, Germany.
Cell Metab. 2011 Jun 8;13(6):720-8. doi: 10.1016/j.cmet.2011.03.021.
Dopaminergic midbrain neurons integrate signals on food palatability and food-associated reward into the complex control of energy homeostasis. To define the role of insulin receptor (IR) signaling in this circuitry, we inactivated IR signaling in tyrosine hydroxylase (Th)-expressing cells of mice (IR(ΔTh)). IR inactivation in Th-expressing cells of mice resulted in increased body weight, increased fat mass, and hyperphagia. While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice. Moreover, these mice exhibited an altered response to cocaine under food-restricted conditions. Taken together, these data provide in vivo evidence for a critical role of insulin signaling in catecholaminergic neurons to control food intake and energy homeostasis.
中脑多巴胺能神经元将食物适口性和与食物相关的奖励信号整合到能量平衡的复杂控制中。为了确定胰岛素受体 (IR) 信号在该回路中的作用，我们在表达酪氨酸羟化酶 (Th) 的小鼠细胞中失活了 IR 信号（IR(ΔTh)）。在表达 Th 的细胞中失活 IR 会导致体重增加、脂肪量增加和多食。虽然胰岛素可急性刺激 50%的多巴胺能 VTA/SN 神经元的放电频率，但在 IR(ΔTh) 小鼠中这种反应被消除。此外，这些小鼠在食物限制条件下对可卡因的反应发生改变。总之，这些数据为胰岛素信号在控制食物摄入和能量平衡的儿茶酚胺能神经元中的关键作用提供了体内证据。
