Pro-opiomelanocortin (POMC) deficiency and peripheral melanocortins in obesity

Melanocortin peptides, derived from pro-opio-melanocortin (POMC), appear to play a significant role in appetite and body weight regulation. Expression of the Pome gene in the central nervous system results in the production o f melanocortin peptides, which bind to the melanocortin-4 receptor (MC4-R) and inhibit food intake, MC4-R knockout mice exhibit adult-onset obesity, w hereas MC4-R agonists suppress food intake in several models of obesity. Re cently, Pome knockout mice were generated and shown to develop hyperphagia and obesity with a time-course and severity comparable to MC4-R knockout mi ce, whereas daily administration of a stable a-melanocyte stimulating hormo ne analogue reversed this effect These data clearly implicate POMC peptides and melanocortin receptors in the pathophysiology of obesity and provide i mportant new tools for their development as therapeutic targets in obesity.