Regulation of muscle fiber type and running endurance by PPARδ

Yong Xu Wang, Chun Li Zhang, Ruth T. Yu, Helen K. Cho, Michael C. Nelson, Corinne R. Bayuga-Ocampo, Jungyeob Ham, Heonjoong Kang, Ronald M. Evans

Research output: Contribution to journalArticle

817 Scopus citations

Abstract

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 δ (PPARδ) 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.

Original languageEnglish (US)
JournalPLoS biology
Volume2
Issue number10
DOIs
StatePublished - Oct 2004

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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