The Transcriptional Coactivator PGC-1β Drives the Formation of Oxidative Type IIX Fibers in Skeletal Muscle

Zoltan Arany, Nathan Lebrasseur, Carl Morris, Eric Smith, Wenli Yang, Yanhong Ma, Sherry Chin, Bruce M. Spiegelman

Research output: Contribution to journalArticle

274 Scopus citations

Abstract

Skeletal muscle must perform different kinds of work, and distinct fiber types have evolved to accommodate these. Previous work had shown that the transcriptional coactivator PGC-1α drives the formation of type I and IIA muscle fibers, which are "slow-twitch" and highly oxidative. We show here that transgenic expression of PGC-1β, a coactivator functionally similar to but distinct from PGC-1α, causes a marked induction of IIX fibers, which are oxidative but have "fast-twitch" biophysical properties. PGC-1β coactivates the MEF2 family of transcription factors to stimulate the type IIX myosin heavy chain (MHC) promoter. PGC-1β transgenic muscle fibers are rich in mitochondria and are highly oxidative, at least in part due to coactivation by PGC-1β of ERRα and PPARα. Consequently, these transgenic animals can run for longer and at higher work loads than wild-type animals. Together, these data indicate that PGC-1β drives the formation of highly oxidative fibers containing type IIX MHC.

Original languageEnglish (US)
Pages (from-to)35-46
Number of pages12
JournalCell Metabolism
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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