Abstract
Genetic1,2,3,4,5,6,7,8 and pharmacological6,9,10,11,12 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 hypothalamus13, 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.
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Acknowledgements
We thank D. Weinberg for providing rat Mc3r cDNA and J. Ronan for assistance in the histological evaluation of adipose tissues.
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Chen, A., Marsh, D., Trumbauer, M. et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet 26, 97–102 (2000). https://doi.org/10.1038/79254
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DOI: https://doi.org/10.1038/79254
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