Q J Med 2000; 93: 7-14
© 2000 Association of Physicians
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The role of melanocortin signalling in the control of body weight: evidence from human and murine genetic models
From the Departments of Medicine and Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke's Hospital, University of Cambridge, and 1 Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK
Professor S. O'Rahilly, Departments of Medicine and Clinical Biochemistry, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK
The peptide products of the pro-opiomelanocortin (POMC) gene have established roles in the control of physiological processes as diverse as adrenal steroidogenesis, skin pigmentation, analgesia and inflammation. In the last 5 years, evidence accumulated from murine and human genetic models of disrupted melanocortin signalling has firmly established a central role for a population of hypothalamic neurons expressing POMC in the control of appetite and body weight. Of the five known melanocortin receptors, the MC4R has been most closely linked to body weight regulation. While a-MSH is active at this receptor and suppresses appetite after central injection, important roles for other POMC-derived products have not been excluded. The development of pharmacological agonists acting on, or mimicking, the hypothalamic melanocortinergic pathway may provide exciting opportunities for the therapy of human obesity.
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