20 years of leptin: connecting leptin signaling to biological function.
20 years of leptin: connecting leptin signaling to biological function.
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DOI：
10.1530/joe-14-0404
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Myers MG Jr
中科院分区：
文献类型：
--
作者：
Allison MB;Myers MG Jr
下丘脑瘦素的作用促进负能量平衡，调节葡萄糖稳态，并作为控制生长和繁殖的神经内分泌轴的许可信号。自从20年前首次发现瘦素以来，我们已经对瘦素作用的分子机制有了大量的了解。其中一个重要的方面是对瘦素信号传导的细胞机制的解剖，以及特定的瘦素信号如何影响生理学。瘦素通过瘦素受体LepRb的长链起作用。LepRb激活和随后的酪氨酸磷酸化招募并激活多种信号通路，包括STAT转录因子、SHP2和ERK信号、IRS-protein/PI3Kinase通路和SH2B1。这些途径中的每一个都控制着瘦素作用和生理的特定方面。由细胞因子信号抑制因子（SOCS）蛋白和蛋白酪氨酸磷酸酶（PTPases）介导的重要抑制途径也限制了生理性瘦素的作用。本文综述了LepRb参与的信号通路及其对能量平衡、葡萄糖稳态和生殖的影响。特别强调的是已用于阐明这些功能在体内的多种小鼠模型。
Hypothalamic leptin action promotes negative energy balance and modulates glucose homeostasis, as well as serving as a permissive signal to the neuroendocrine axes that control growth and reproduction. Since the initial discovery of leptin 20 years ago, we have learned a great deal about the molecular mechanisms of leptin action. An important aspect of this has been the dissection of the cellular mechanisms of leptin signaling, and how specific leptin signals influence physiology. Leptin acts via the long form of the leptin receptor, LepRb. LepRb activation and subsequent tyrosine phosphorylation recruits and activates multiple signaling pathways, including STAT transcription factors, SHP2 and ERK signaling, the IRS-protein/PI3Kinase pathway, and SH2B1. Each of these pathways controls specific aspects of leptin action and physiology. Important inhibitory pathways mediated by suppressor of cytokine signaling (SOCS) proteins and protein tyrosine phosphatases (PTPases) also limit physiologic leptin action. This review summarizes the signaling pathways engaged by LepRb and their effects on energy balance, glucose homeostasis, and reproduction. Particular emphasis is given to the multiple mouse models which have been used to elucidate these functions in vivo.