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。
Hypotha is the center of energy homeostasis in the organism. The central step of its endocrinology regulation network is that it can receive the leptin signal provided by peripheral adipose tissues,and subsequently modulate the expression of Agouti-related protein (AgRP) and proopiomelanocortin (POMC), maintaining energy homeostasis by regulating energy intake and consumption. Transcription factors FoxO1 and STAT3 (signal transducer and activator of transcription 3) are key molecules in leptin mediated transcriptional regulation of AgRP; they directly participate in the regulation of energy homeostasis. FoxO1 can enhance AgRP expression and activated STAT3 can inhibit AgRP expression. Leptin can modulate AgRP and energy homeostasis through inhibiting FoxO1 activity and activating STAT3. The article reviews the regulatory mechanism of leptin upon AgRP.