Nature Medicine
5, 1066 - 1070 (1999)
doi:10.1038/12506
Obesity in the mouse model of pro-opiomelanocortin deficiency responds
to peripheral melanocortinLinda Yaswen1, 4, Nicole Diehl1, 5, Miles B. Brennan2
& Ute Hochgeschwender31
Unit on Molecular Genetics, Clinical Neuroscience Branch, NIMH, 49 Convent Drive, Bethesda, Maryland 20892,USA
2
Eleanor Roosevelt Institute, 1899 Gaylord Street, Denver, Colorado 80206, USA
3
Developmental Biology Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma 73104, USA
4
L.Y. present address: Metamorphix, 1450 South Rolling Road, Baltimore, Maryland 21227, USA
5
N.D. present address: University of Vermont, Given C-321, Burlington, Vermont 05405, USA
Correspondence should be addressed to Ute Hochgeschwender uteh@omrf.ouhsc.eduPro-opiomelanocortin (POMC)-derived peptides (the melanocortins adrenocorticotropin,  -,  -
and  -melanocyte stimulating hormone; and the endogenous opioid -endorphin)
have a diverse array of biological activities, including roles in pigmentation,
adrenocortical function and regulation of energy stores, and in the immune
system and the central and peripheral nervous systems1. We show
here that mice lacking the POMC-derived peptides have obesity, defective adrenal
development and altered pigmentation. This phenotype is similar to that of
the recently identified human POMC-deficient patients2. When
treated with a stable -melanocyte-stimulating hormone agonist, mutant
mice lost more than 40% of their excess weight after 2 weeks. Our results
identify the POMC-null mutant mouse as a model for studying the human POMC-null
syndrome, and indicate the therapeutic use of peripheral melanocortin in the
treatment of obesity.
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