Regulation of Muscle Fiber Type and Running Endurance by PPARδ

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 delta (PPARdelta) in skeletal muscle, which induces a switch to form increased numbers of type I muscle fibers. Treatment of wild-type mice with PPARdelta agonist elicits a similar type I fiber gene expression profile in…

• HH
  Howard Hughes Medical Institute
• MO
  March of Dimes Foundation
• LL
  Larry L. Hillblom Foundation
• TD
  Tobacco-Related Disease Research Program