The role of melanocortin signalling in the control of body weight: evidence from human and murine genetic models

The peptide products of the pro-opiomelanocortin (POMC) gene have establish ed roles in the control of physiological processes as diverse as adrenal st eroidogenesis, skin pigmentation, analgesia and inflammation. In the last 5 years, evidence accumulated from murine and human genetic models of disrup ted melanocortin signalling has firmly established a central role for a pop ulation of hypothalamic neurons expressing POMC in the control of appetite and body weight. Of the five known melanocortin receptors, the MC4R has bee n most closely linked to body weight regulation. While alpha-MSH is active at this receptor and suppresses appetite after central injection, important roles for other POMC-derived products have not been excluded. The developm ent of pharmacological agonists acting on, or mimicking, the hypothalamic m elanocortinergic pathway may provide exciting opportunities for the therapy of human obesity.