Morris David L, Rui Liangyou
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Mchigan 48109-0622, USA.
Am J Physiol Endocrinol Metab. 2009 Dec;297(6):E1247-59. doi: 10.1152/ajpendo.00274.2009. Epub 2009 Sep 1.
The brain controls energy homeostasis and body weight by integrating various metabolic signals. Leptin, an adipose-derived hormone, conveys critical information about peripheral energy storage and availability to the brain. Leptin decreases body weight by both suppressing appetite and promoting energy expenditure. Leptin directly targets hypothalamic neurons, including AgRP and POMC neurons. These leptin-responsive neurons widely connect to other neurons in the brain, forming a sophisticated neurocircuitry that controls energy intake and expenditure. The anorexigenic actions of leptin are mediated by LEPRb, the long form of the leptin receptor, in the hypothalamus. LEPRb activates both JAK2-dependent and -independent pathways, including the STAT3, PI 3-kinase, MAPK, AMPK, and mTOR pathways. These pathways act coordinately to form a network that fully mediates leptin response. LEPRb signaling is regulated by both positive (e.g., SH2B1) and negative (e.g., SOCS3 and PTP1B) regulators and by endoplasmic reticulum stress. Leptin resistance, a primary risk factor for obesity, likely results from impairment in leptin transport, LEPRb signaling, and/or the neurocircuitry of energy balance.
大脑通过整合各种代谢信号来控制能量平衡和体重。瘦素是一种源自脂肪组织的激素，它将有关外周能量储存和可利用性的关键信息传递给大脑。瘦素通过抑制食欲和促进能量消耗来减轻体重。瘦素直接作用于下丘脑神经元，包括AgRP神经元和POMC神经元。这些对瘦素敏感的神经元广泛连接到大脑中的其他神经元，形成一个复杂的神经回路，控制能量摄入和消耗。瘦素的厌食作用由下丘脑的瘦素受体长型（LEPRb）介导。LEPRb激活JAK2依赖和非依赖途径，包括STAT3、PI 3激酶、MAPK、AMPK和mTOR途径。这些途径协同作用形成一个网络，完全介导瘦素反应。LEPRb信号传导受到正向调节因子（如SH2B1）和负向调节因子（如SOCS3和PTP1B）以及内质网应激的调节。瘦素抵抗是肥胖的主要危险因素，可能是由于瘦素转运、LEPRb信号传导和/或能量平衡神经回路受损所致。
