Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition Research Center, UMR-S 1172, Lille, 59000, France.
University of Lille, FHU 1,000 Days for Health, Lille, 59000, France.
Exp Mol Med. 2022 Apr;54(4):403-413. doi: 10.1038/s12276-021-00625-8. Epub 2022 Apr 26.
The melanocortin system plays a critical role in the central regulation of food intake and energy balance. This system consists of neurons producing pro-opiomelanocortin (POMC), melanocortin receptors (MC4Rs), and the endogenous antagonist agouti-related peptide (AgRP). Pomc and Mc4r deficiency in rodents and humans causes early onset of obesity, whereas a loss of Agrp function is associated with leanness. Accumulating evidence shows that many chronic diseases, including obesity, might originate during early life. The melanocortin system develops during a relatively long period beginning during embryonic life with the birth of POMC and AgRP neurons and continuing postnatally with the assembly of their neuronal circuitry. The development of the melanocortin system requires the tight temporal regulation of molecular factors, such as transcription factors and axon guidance molecules, and cellular mechanisms, such as autophagy. It also involves a complex interplay of endocrine and nutritional factors. The disruption of one or more of these developmental factors can lead to abnormal maturation and function of the melanocortin system and has profound metabolic consequences later in life.
黑皮质素系统在中枢对食物摄入和能量平衡的调节中起着关键作用。该系统由产生前阿黑皮素原（POMC）的神经元、黑皮质素受体（MC4Rs）和内源性拮抗剂刺鼠相关蛋白（AgRP）组成。啮齿动物和人类中 POMC 和 Mc4r 的缺失会导致肥胖的早期发病，而 Agrp 功能的丧失则与消瘦有关。越来越多的证据表明，包括肥胖在内的许多慢性疾病可能起源于生命早期。黑皮质素系统在相对较长的时间内发育，从胚胎生命开始产生 POMC 和 AgRP 神经元，并在出生后继续形成其神经元回路。黑皮质素系统的发育需要分子因素（如转录因子和轴突导向分子）和细胞机制（如自噬）的严格时间调节。它还涉及内分泌和营养因素的复杂相互作用。这些发育因素中的一个或多个的破坏会导致黑皮质素系统的异常成熟和功能，并对以后的生活产生深远的代谢后果。
