University Departments of Medicine and Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom
Correspondence: Address all correspondence and requests for reprints to: Stephen O’Rahilly, University Departments of Medicine and Clinical Biochemistry, Box 232, Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom. E-mail: so104{at}medschl.cam.ac.uk
Considerable attention has focused on deciphering the hypothalamicpathways that mediate the behavioral and metabolic effects ofleptin. We and others have identified several single gene defectsthat disrupt the molecules in the leptin-melanocortin pathwaycausing severe obesity in humans. In this review, we considerthese human monogenic obesity syndromes and discuss how farthe characterization of these patients has informed our understandingof the physiological role of leptin and the melanocortins inthe regulation of human body weight and neuroendocrine function.
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