60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH.
60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH.
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DOI：
10.1530/jme-16-0014
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发表时间：
2016-05
影响因子：
3.5
通讯作者：
Litt MJ
中科院分区：
文献类型：
--
作者：
Anderson EJ;Çakir I;Carrington SJ;Cone RD;Ghamari-Langroudi M;Gillyard T;Gimenez LE;Litt MJ
源自阿片黑皮质素原 (POMC) 的黑皮质素肽最初是根据 α-黑素细胞刺激激素 (α-MSH) 对色素沉着的生物学作用和促肾上腺皮质激素对肾上腺皮质糖皮质激素产生的生物学作用来理解的。然而，中枢神经系统中 POMC mRNA 和黑皮质素肽的发现引发了旨在了解黑皮质素在大脑中的直接生物学作用的活动。最终，中枢神经系统中表达的独特黑皮质素受体，即黑皮质素-3 (MC3R) 和黑皮质素-4 (MC4R) 受体的发现，促进了药理学工具和遗传模型的发展，从而证明中枢黑皮质素系统在能量稳态调节中发挥着关键作用。事实上，现在已知 MC4R 突变是早发综合征性肥胖的最常见原因，占所有病例的 2-5%。这篇综述讨论了这些发现的历史，以及试图了解中枢神经系统中主要黑皮质素肽 α-MSH 调节摄食和能量稳态的分子和细胞基础的最新工作。
The melanocortin peptides derived from pro-opiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte-stimulating hormone (α-MSH) on pigmentation and adrenocorticotrophic hormone on adrenocortical glucocorticoid production. However, the discovery of POMC mRNA and melanocortin peptides in the CNS generated activities directed at understanding the direct biological actions of melanocortins in the brain. Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the development of pharmacological tools and genetic models leading to the demonstration that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Indeed, mutations in MC4R are now known to be the most common cause of early onset syndromic obesity, accounting for 2–5% of all cases. This review discusses the history of these discoveries, as well as the latest work attempting to understand the molecular and cellular basis of regulation of feeding and energy homeostasis by the predominant melanocortin peptide in the CNS, α-MSH.