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


Journal Article

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.

Full Text

Cited Authors

  • Forbes, S; Bui, S; Robinson, BR; Hochgeschwender, U; Brennan, MB

Published Date

  • March 20, 2001

Published In

Volume / Issue

  • 98 / 7

Start / End Page

  • 4233 - 4237

PubMed ID

  • 11259669

Pubmed Central ID

  • 11259669

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.071054298


  • eng