| Literature DB >> 10973258 |
A S Chen1, D J Marsh, M E Trumbauer, E G Frazier, X M Guan, H Yu, C I Rosenblum, A Vongs, Y Feng, L Cao, J M Metzger, A M Strack, R E Camacho, T N Mellin, C N Nunes, W Min, J Fisher, S Gopal-Truter, D E MacIntyre, H Y Chen, L H Van der Ploeg.
Abstract
Genetic and pharmacological studies have defined a role for the melanocortin-4 receptor (Mc4r) in the regulation of energy homeostasis. The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown. We evaluated the potential role of Mc3r in energy homeostasis by studying Mc3r-deficient (Mc3r(-/-)) mice and compared the functions of Mc3r and Mc4r in mice deficient for both genes. The 4-6-month Mc3r-/- mice have increased fat mass, reduced lean mass and higher feed efficiency than wild-type littermates, despite being hypophagic and maintaining normal metabolic rates. (Feed efficiency is the ratio of weight gain to food intake.) Consistent with increased fat mass, Mc3r(-/-) mice are hyperleptinaemic and male Mc3r(-/-) mice develop mild hyperinsulinaemia. Mc3r(-/-) mice did not have significantly altered corticosterone or total thyroxine (T4) levels. Mice lacking both Mc3r and Mc4r become significantly heavier than Mc4r(-/-) mice. We conclude that Mc3r and Mc4r serve non-redundant roles in the regulation of energy homeostasis.Entities:
Mesh：
Substances：
Year: 2000 PMID： 10973258 DOI： 10.1038/79254
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330