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 prod...
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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 of melanocortin peptides, which bind to the melanocortin-4 receptor (MC4-R) and inhibit food intake, MC4-R knockout mice exhibit adult-onset obesity, whereas MC4-R agonists suppress food intake in several models of obesity. Recently, Pome knockout mice were generated and shown to develop hyperphagia and obesity with a time-course and severity comparable to MC4-R knockout mice, whereas daily administration of a stable a-melanocyte stimulating hormone analogue reversed this effect These data clearly implicate POMC peptides and melanocortin receptors in the pathophysiology of obesity and provide important new tools for their development as therapeutic targets in obesity.
Pro-opiomelanocortin (POMC)-derived peptides (the melanocortins adrenocorticotropin, alpha-, beta- and gamma-melanocyte stimulating hormone;and the endogenous opioid beta-endorphin) have a diverse array of biological ...
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Pro-opiomelanocortin (POMC)-derived peptides (the melanocortins adrenocorticotropin, alpha-, beta- and gamma-melanocyte stimulating hormone;and the endogenous opioid beta-endorphin) have a diverse array of biological activities, including roles in pigmentation, adrenocortical function and regulation of energy stores, and in the immune system and the central and peripheral nervous systems'. We show here that mice lacking the POMC-derived peptides have obesity, defective adrenal development and altered pigmentation. This phenotype is similar to that of the recently identified human POMC-deficient patients(2). When treated with a stable alpha-melanocyte-stimulating hormone agonist, mutant mice lost more than 40% of their excess weight after 2 weeks. Our results identify the POMC-null mutant mouse as a model for studying the human POMC-null syndrome, and indicate the therapeutic use of peripheral melanocortin in the treatment of obesity.
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