Abstract
Pro-opiomelanocortin (POMC)-derived peptides (the melanocortins adrenocorticotropin, α-, β- and γ-melanocyte stimulating hormone; and the endogenous opioid β-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 α-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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Acknowledgements
We thank J. Elliott and S. Bui for their technical assistance, M. Glynn for art work, B. Martin for oligonucleotide synthesis, E.I. Ginns for support of the early phases of the work and M. Davisson for comments on an earlier version of the manuscript. This work was supported by a generous grant from the Board of Trustees of the Eleanor Roosevelt Institute, Denver, Colorado (M.B.B.) and by the Samuel Roberts Noble Foundation, Ardmore, Oklahoma (U.H.).
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Yaswen, L., Diehl, N., Brennan, M. et al. Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 5, 1066–1070 (1999). https://doi.org/10.1038/12506
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DOI: https://doi.org/10.1038/12506
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