Department of Foods and Nutrition, University of Georgia, Athens, GA 30606, USA.
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90089, USA.
Peptides. 2021 Mar;137:170476. doi: 10.1016/j.peptides.2020.170476. Epub 2020 Dec 25.
Given the increased prevalence of obesity and its associated comorbidities, understanding the mechanisms through which the brain regulates energy balance is of critical importance. The neuropeptide melanin-concentrating hormone (MCH) is produced in the lateral hypothalamic area and the adjacent incerto-hypothalamic area and promotes both food intake and energy conservation, overall contributing to body weight gain. Decades of research into this system has provided insight into the neural pathways and mechanisms (behavioral and neurobiological) through which MCH stimulates food intake. Recent technological advancements that allow for selective manipulation of MCH neuron activity have elucidated novel mechanisms of action for the hyperphagic effects of MCH, implicating neural "volume" transmission in the cerebrospinal fluid and sex-specific effects of MCH on food intake control as understudied areas for future investigation. Highlighted here are historical and recent findings that illuminate the neurobiological mechanisms through which MCH promotes food intake, including the identification of various specific neural signaling pathways and interactions with other peptide systems. We conclude with a framework that the hyperphagic effects of MCH signaling are predominantly mediated through enhancement of an "appetition" process in which early postoral prandial signals promote further caloric consumption.
鉴于肥胖症及其相关合并症的患病率不断增加，了解大脑调节能量平衡的机制至关重要。神经肽黑素浓缩激素 (MCH) 在外侧下丘脑区域和相邻的下丘脑神经核区域产生，促进食物摄入和能量保存，总体上导致体重增加。几十年来对该系统的研究深入了解了 MCH 刺激食物摄入的神经通路和机制（行为和神经生物学）。最近的技术进步允许选择性地操纵 MCH 神经元活动，阐明了 MCH 促食作用的新作用机制，表明神经“容积”传递在脑脊液中以及 MCH 对食物摄入控制的性别特异性影响是未来研究的未充分研究领域。本文重点介绍了阐明 MCH 促进食物摄入的神经生物学机制的历史和最新发现，包括确定各种特定的神经信号通路以及与其他肽系统的相互作用。我们最后提出了一个框架，即 MCH 信号的促食作用主要是通过增强“食欲”过程来介导的，其中早期口腔后进食信号促进进一步的热量消耗。
