regulation of muscle fiber type and running endurance by pparδ肌纤维类型和运行监管pparδ耐力.pdfVIP

Open access, freely available online PLoS BIOLOGY Regulation of Muscle Fiber Type and Running Endurance by PPARd 1 1 1 1 1,2 1 Yong-Xu Wang , Chun-Li Zhang , Ruth T. Yu , Helen K. Cho , Michael C. Nelson , Corinne R. Bayuga-Ocampo , Jungyeob Ham3 3 1,2* , Heonjoong Kang , Ronald M. Evans 1 Gene Expression Laboratory, Salk Institute, La Jolla, California, United States of America, 2 Howard Hughes Medical Institute, La Jolla, California, United States of America, 3 Marine Biotechnology Laboratory, School of Earth and Environmental Sciences, Seoul National University, Seoul, Korea Endurance exercise training can promote an adaptive muscle fiber transformation and an increase of mitochondrial biogenesis by triggering scripted changes in gene expression. However, no transcription factor has yet been identified that can direct this process. We describe the engineering of a mouse capable of continuous running of up to twice the distance of a wild-type littermate. This was achieved by targeted expression of an activated form of peroxisome proliferator-activated receptor d (PPARd) in skeletal muscle, which induces a switch to form increased numbers of type I muscle fibers. Treatment of wild-type mice with PPARd agonist elicits a similar type I fiber gene expression profile in muscle. Moreover, these genetically generated fibers confer resistance to obesity with improved metabolic profiles, even in the absence of exercise. These results demonstrate that complex physiologic properties such as fatigue, endurance, and running capacity can be molecularly analyzed and manipulated. Citation: Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC, et al. (2004) Regulation of muscle fiber type and running endurance