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下丘脑是机体能量代谢的调节中枢,其神经内分泌调节网络的中心环节是感受外周脂肪细胞分泌的瘦素所提供的能量贮存信号,调控下丘脑弓状核内Agouti相关蛋白(AgRP)和阿黑皮素原(POMC)的表达水平,从而调节能量的摄入和消耗,维持机体能量代谢的稳态。转录因子叉头框蛋白1(FoxO1)和信号转导及转录激活因子3(STAT3)是介导瘦素对AgRP转录调控作用的重要分子,直接参与了机体能量代谢的稳态调节。FoxO1可以增强AgRP的转录活性,而STAT3活化后则抑制AgRP的转录水平。瘦素可通过抑制FoxO1和激活STAT3实现对AgRP和能量代谢的调控。本文就瘦素对AgRP基因的转录调控机制的最新进展作一综述。
The hypothalamus is the central regulator of the body’s energy metabolism. The central part of the neuroendocrine regulation network is to sense the energy storage signal provided by the leptin secreted by the peripheral adipocytes, regulate the Agouti-related protein (AgRP) in the arcuate nucleus of the hypothalamus, The expression level of POMC regulates the energy intake and consumption and maintains the homeostasis of energy metabolism. Transcriptional Factors FoxO1 and STAT3 are important molecules that mediate the transcriptional regulation of AgRP by leptin, and are directly involved in homeostasis of energy metabolism. FoxO1 can enhance the transcriptional activity of AgRP, while STAT3 activation inhibits AgRP transcription. Leptin can regulate AgRP and energy metabolism by inhibiting FoxO1 and activating STAT3. This review summarizes the latest progress of leptin on the transcriptional regulation of AgRP gene.