Irani B G, Xiang Z, Moore M C, Mandel R J, Haskell-Luevano C
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, P.O. Box 100485, Gainesville, FL 32610, USA.
Biochem Biophys Res Commun. 2005 Jan 21;326(3):638-44. doi: 10.1016/j.bbrc.2004.11.084.
The melanocortin system is involved in hypothalamic regulation of energy homeostasis. The melanocortin-4 receptor (MC4R) has been linked to both obesity and reproductive dysfunction. Deletion of the MC4R from the mouse genome has resulted in phenotypes including adult onset obesity, hyperphagia, and difficulty in reproducing when homozygote parents are bred. Additionally, polymorphisms of the human MC4R have been identified in morbidly obese children and adults. Herein, we have identified that voluntary exercise, provided via the presence of a running wheel, impedes the monogenetic obesity (at 20 weeks of age running wheel housed body weight=31+/-1.8 g versus conventionally housed body weight=41+/-2.3 g, a 25% decrease in body weight p<0.01), hyperphagia (average cumulative food intake is not statistically different than wild type mice housed in running wheel cages), and reproductive dysfunction phenotypes associated with the MC4R knockout mice housed by conventional means. These data demonstrate the novel finding that voluntary exercise at a young age may hinder genetically induced obesity.
黑皮质素系统参与下丘脑对能量平衡的调节。黑皮质素-4受体（MC4R）与肥胖和生殖功能障碍均有关联。从小鼠基因组中删除MC4R会导致一些表型，包括成年后发病的肥胖、食欲亢进，以及纯合子亲本繁殖时出现繁殖困难。此外，在病态肥胖的儿童和成人中已发现人类MC4R的多态性。在此，我们发现通过放置跑轮提供的自愿运动可抑制单基因肥胖（20周龄时，有跑轮的小鼠体重=31±1.8克，而常规饲养的小鼠体重=41±2.3克，体重下降25%，p<0.01）、食欲亢进（平均累积食物摄入量与饲养在有跑轮笼子里的野生型小鼠无统计学差异），以及与常规饲养的MC4R基因敲除小鼠相关的生殖功能障碍表型。这些数据证明了一个新发现，即幼年时的自愿运动可能会阻碍基因诱导的肥胖。
