Wyeth Research, CN 8000, Princeton, NJ 08540, USA.
J Mol Neurosci. 2009 Sep;39(1-2):86-98. doi: 10.1007/s12031-009-9207-6. Epub 2009 May 6.
The melanin-concentrating hormone (MCH) is a cyclic peptide exerting its actions through two G-protein-coupled receptors, MCHR1 and MCHR2. MCH is implicated in the regulation of different physiological functions, including energy homeostasis and mood that is supported by the distribution of MCH and MCHR1 in the hypothalamus as well as corticolimbic structures. Genetic manipulation of MCH and MCHR1 results in a lean phenotype with increased resting energy expenditure as well as anxiolytic and antidepressant phenotypes. Similar observations have been demonstrated pharmacologically using different classes of selective MCHR1 antagonists. Here, we summarize the reported genetic and pharmacological evidence for the role played by the MCH system in the regulation of both energy homeostasis and mood disorders. We also comment on the utility of small-molecule MCHR1 antagonists for the treatment of obesity and affective disorders compared to existing therapies and provide a critical overview of the potential risks.
黑色素浓缩激素（MCH）是一种环状肽，通过两种 G 蛋白偶联受体（MCHR1 和 MCHR2）发挥作用。MCH 参与调节多种生理功能，包括能量平衡和情绪，这一点得到了 MCH 和 MCHR1 在下丘脑以及皮质边缘结构中的分布的支持。对 MCH 和 MCHR1 的遗传操作导致了一种瘦体型，表现为静息能量消耗增加，以及抗焦虑和抗抑郁表型。使用不同类别的选择性 MCHR1 拮抗剂进行药理学研究也得到了类似的观察结果。在这里，我们总结了 MCH 系统在调节能量平衡和情绪障碍方面的作用的报道的遗传和药理学证据。我们还评论了与现有疗法相比，小分子 MCHR1 拮抗剂在治疗肥胖症和情感障碍方面的应用，并对潜在风险进行了批判性概述。
