Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin

Pro-opiomelanocortin (POMC)-derived peptides (the melanocortins adrenocorti cotropin, alpha-, beta- and gamma-melanocyte stimulating hormone; and the e ndogenous opioid beta-endorphin) have a diverse array of biological activit ies, including roles in pigmentation, adrenocortical function and regulatio n 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-deficie nt patients(2). When treated with a stable alpha-melanocyte-stimulating hor mone 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 stud ying the human POMC-null syndrome, and indicate the therapeutic use of peri pheral melanocortin in the treatment of obesity.