Kaelin C B, Candille S I, Yu B, Jackson P, Thompson D A, Nix M A, Binkley J, Millhauser G L, Barsh G S
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Int J Obes (Lond). 2008 Dec;32 Suppl 7:S19-27. doi: 10.1038/ijo.2008.234.
Named originally for their effects on peripheral end organs, the melanocortin system controls a diverse set of physiological processes through a series of five G-protein-coupled receptors and several sets of small peptide ligands. The central melanocortin system plays an essential role in homeostatic regulation of body weight, in which two alternative ligands, alpha-melanocyte-stimulating hormone and agouti-related protein, stimulate and inhibit receptor signaling in several key brain regions that ultimately affect food intake and energy expenditure. Much of what we know about the relationship between central melanocortin signaling and body weight regulation stems from genetic studies. Comparative genomic studies indicate that melanocortin receptors used for controlling pigmentation and body weight regulation existed more than 500 million years ago in primitive vertebrates, but that fine-grained control of melanocortin receptors through neuropeptides and endogenous antagonists developed more recently. Recent studies based on dog coat-color genetics revealed a new class of melanocortin ligands, the beta-defensins, which reveal the potential for cross talk between the melanocortin and the immune systems.
黑皮质素系统最初因其对周围终末器官的作用而得名，它通过一系列五种G蛋白偶联受体和几组小肽配体来控制多种生理过程。中枢黑皮质素系统在体重的稳态调节中起着至关重要的作用，其中两种替代配体，α-黑素细胞刺激素和刺鼠相关蛋白，在几个关键脑区刺激和抑制受体信号传导，最终影响食物摄入和能量消耗。我们对中枢黑皮质素信号传导与体重调节之间关系的许多了解都源于遗传学研究。比较基因组研究表明，用于控制色素沉着和体重调节的黑皮质素受体在5亿多年前就存在于原始脊椎动物中，但通过神经肽和内源性拮抗剂对黑皮质素受体的精细控制是最近才发展起来的。基于犬类毛色遗传学的最新研究揭示了一类新的黑皮质素配体，即β-防御素，它揭示了黑皮质素系统与免疫系统之间相互作用的潜力。
