Understanding the complex action mechanism of appetite regulation peptides can significantly impact therapeutic options in the treatment of obesity and other metabolic diseases. Hypothalamic α-melanocyte-stimulating hormone (α-MSH) is an anorexigenic peptide, closely related to the occurrence of obesity, playing a central role in food intake and energy expenditure. In the central nervous system (CNS), α-MSH is cleaved from proopiomelanocortin (POMC) and then released into different hypothalamic regions to act on melanocortin 3/4 receptor (MC3/4R)-expressing neurons, lowering food intake and raising energy expenditure via appetite suppression and sympathetic nervous system. Furthermore, it can increase the transmission of some anorexigenic hormones (e.g., dopamine) and interact with other orexigenic factors (e.g., agouti-related protein, neuropeptide Y) to influence food reward rather than merely feeding behavior. Therefore, α-MSH is a critical node of the hypothalamus in transmitting appetite suppression signals and is a key component of the central appetite-regulating circuits. Herein, we describe the role of α-MSH in appetite suppression in terms of specific receptors, effector neurons, sites of action, and the interaction with other appetite-relative peptides, respectively. We focus on the role of α-MSH in obesity. The status of research on α-MSH-related drugs is also discussed. With the intention of illuminating a new approach for targeting α-MSH in the hypothalamus as a strategy to manage obesity, we hope to further understand the direct or indirect mechanisms by which α-MSH exerts its appetite-regulating effects.


中文翻译：

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中枢神经系统中α-黑素细胞刺激激素介导的食欲调节

了解食欲调节肽的复杂作用机制可以显着影响肥胖和其他代谢疾病的治疗选择。下丘脑α-黑素细胞刺激激素（α-MSH）是一种厌食肽，与肥胖的发生密切相关，在食物摄入和能量消耗中发挥着核心作用。在中枢神经系统 (CNS) 中，α-MSH 从阿片黑皮质素原 (POMC) 中裂解下来，然后释放到下丘脑的不同区域，作用于表达黑皮质素 3/4 受体 (MC3/4R) 的神经元，从而降低食物摄入量并增加能量消耗通过食欲抑制和交感神经系统。此外，它可以增加一些促食欲激素（例如多巴胺）的传递，并与其他促食欲因子（例如刺豚鼠相关蛋白、神经肽Y）相互作用以影响食物奖励而不仅仅是进食行为。因此，α-MSH是下丘脑传递食欲抑制信号的关键节点，是中枢食欲调节回路的关键组成部分。在此，我们分别从特定受体、效应神经元、作用位点以及与其他食欲相关肽的相互作用方面描述了 α-MSH 在食欲抑制中的作用。我们重点关注 α-MSH 在肥胖中的作用。还讨论了α-MSH相关药物的研究现状。为了阐明一种靶向下丘脑 α-MSH 作为治疗肥胖策略的新方法，我们希望进一步了解 α-MSH 发挥食欲调节作用的直接或间接机制。