regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system精益质量监管、骨量和运动耐量由中央肾上腺皮质系统.pdfVIP

Regulation of Lean Mass, Bone Mass, and Exercise Tolerance by the Central Melanocortin System 1,2. 4. 1 1 1 Theodore P. Braun , Benjamin Orwoll , Xinxia Zhu , Peter R. Levasseur , Marek Szumowski , My 1 5 3 1 Linh T. Nguyen , Mary L. Bouxsein , Robert F. Klein , Daniel L. Marks * ´ 1 Pape Family Pediatric Research Institute, Oregon Health Science University, Portland, Oregon, United States of America, 2 MD/PhD Program, Oregon Health Science University, Portland, Oregon, United States of America, 3 Bone and Mineral Unit, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health Science University, Portland, Oregon, United States of America, 4 Department of Pediatrics, Loma Linda University, Loma Linda, California, United States of America, 5 Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America Abstract Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO). We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO) wild type mice