Claret Marc, Haddad-Tóvolli Roberta
Neuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
Rev Endocr Metab Disord. 2025 Jun 24. doi: 10.1007/s11154-025-09983-4.
The melanocortin system is fundamental for the regulation of whole-body energy homeostasis. This system consists of pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARH), as well as downstream neurons expressing melanocortin receptors (MCRs) located in various brain regions. Emerging evidence highlights significant anatomical and functional sex differences within the melanocortin system, influencing sex-dimorphic metabolic adaptations, the regulation of appetite and energy expenditure and susceptibility to metabolic conditions. These differences are primarily shaped by sex hormones, genetic and environmental factors as well as distinct neurocircuitry organization between males and females. These sex-specific regulatory mechanisms have important implications for the pathophysiology of metabolic disorders, including obesity, type 2 diabetes, and eating disorders. In this review, we explore current knowledge on sex differences in the development and function of the melanocortin system and how this is translated into sex-dimorphic control of metabolism. This emphasizes the need to incorporate sex as a critical variable in both metabolic research and clinical studies. Understanding these mechanisms may provide more precise and effective therapeutic strategies for metabolic disorders, obesity, and appetite dysregulation in both sexes.
黑皮质素系统对于全身能量稳态的调节至关重要。该系统由下丘脑弓状核（ARH）中的阿黑皮素原（POMC）和刺鼠相关肽（AgRP）神经元，以及位于各个脑区表达黑皮质素受体（MCRs）的下游神经元组成。新出现的证据突显了黑皮质素系统内显著的解剖学和功能性别差异，这些差异影响着性别二态性代谢适应、食欲和能量消耗的调节以及对代谢状况的易感性。这些差异主要由性激素、遗传和环境因素以及雄性和雌性之间不同的神经回路组织所塑造。这些性别特异性调节机制对包括肥胖症、2型糖尿病和饮食失调在内的代谢紊乱的病理生理学具有重要意义。在本综述中，我们探讨了关于黑皮质素系统发育和功能中性别差异的现有知识，以及这如何转化为对代谢的性别二态性控制。这强调了在代谢研究和临床研究中都需要将性别作为一个关键变量纳入考虑。了解这些机制可能为两性的代谢紊乱、肥胖症和食欲失调提供更精确有效的治疗策略。
