Integrated control of appetite and fat metabolism by the leptin-proopiomelanocortin pathway

Stacy Forbes, Stephanie Bui, Brian R. Robinson, Ute Hochgeschwender, Miles B. Brennan

Research output: Contribution to journalArticlepeer-review

120 Scopus citations


Leptin deficiency results in a complex obesity phenotype comprising both hyperphagia and lowered metabolism. The hyperphagia results, at least in part, from the absence of induction by leptin of melanocyte stimulating hormone (MSH) secretion in the hypothalamus; the MSH normally then binds to melanocortin-4 receptor expressing neurons and inhibits food intake. The basis for the reduced metabolic rate has been unknown. Here we show that leptin administered to leptin-deficient (ob/ob) mice results in a large increase in peripheral MSH levels; further, peripheral administration of an MSH analogue results in a reversal of their abnormally low metabolic rate, in an acceleration of weight loss during a fast, in partial restoration of thermoregulation in a cold challenge, and in inducing serum free fatty acid levels. These results support an important peripheral role for MSH in the integration of metabolism with appetite in response to perceived fat stores indicated by leptin levels.

Original languageEnglish
Pages (from-to)4233-4237
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Mar 27 2001


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