The transcriptional coactivator PGC-1β drives the formation of oxidative type IIX fibers in skeletal muscle

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-1 alpha 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-1 beta, a coactivator functionally similar to but distinct from PGC-1 alpha, causes a marked induction of IN fibers, which are oxidative but have fast-twitch biophysical properties. PGC-1 beta coactivates the MEF2 family of transcription factors to stimulate the type IIX myosin heavy chain (MHC) promoter. PGC-1 beta transgenic muscle fibers are rich in mitochondria and are highly oxidative, at least in part due to coactivation by PGC-1 beta of ERR alpha and PPAR alpha. Consequently, these transgenic animals can run for longer and at higher work loads than wild-type animals. Together, these data indicate that PGC-1 beta drives the formation of highly oxidative fibers containing type IIX MHC.