Chen A S, Marsh D J, Trumbauer M E, Frazier E G, Guan X M, Yu H, Rosenblum C I, Vongs A, Feng Y, Cao L, Metzger J M, Strack A M, Camacho R E, Mellin T N, Nunes C N, Min W, Fisher J, Gopal-Truter S, MacIntyre D E, Chen H Y, Van der Ploeg L H
Department of Obesity Research, Merck Research Laboratories, Rahway, New Jersey, USA.
Nat Genet. 2000 Sep;26(1):97-102. doi: 10.1038/79254.
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.
遗传学和药理学研究已确定黑皮质素-4受体（Mc4r）在能量平衡调节中发挥作用。黑皮质素受体3（Mc3r）在下丘脑中高水平表达，但其生理功能尚不清楚。我们通过研究Mc3r基因缺陷（Mc3r(-/-)）小鼠，评估了Mc3r在能量平衡中的潜在作用，并比较了Mc3r和Mc4r在两种基因均缺陷的小鼠中的功能。4至6个月大的Mc3r-/-小鼠尽管摄食量减少且维持正常代谢率，但与野生型同窝小鼠相比，脂肪量增加、瘦体重减少且饲料效率更高。（饲料效率是体重增加与食物摄入量的比值。）与脂肪量增加一致，Mc3r(-/-)小鼠血中瘦素水平升高，雄性Mc3r(-/-)小鼠出现轻度高胰岛素血症。Mc3r(-/-)小鼠的皮质酮或总甲状腺素（T4）水平无显著变化。同时缺乏Mc3r和Mc4r的小鼠比Mc4r(-/-)小鼠明显更重。我们得出结论，Mc3r和Mc4r在能量平衡调节中发挥非冗余作用。
