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-1a 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-1b, a coactivator functionally similar to but distinct from PGC-1a, causes a marked induction of IIX fibers, which are oxidative but have ‘‘fast-twitch’’ biophysical properties. PGC-1b coactivates the MEF2 family of transcription factors to stimulate the type IIX myosin heavy chain (MHC) promoter. PGC-1b transgenic muscle fibers are rich in mitochondria and are highly oxidative, at least in part due to coactivation by PGC-1b of ERRa and PPARa. Consequently, these transgenic animals can run for longer and at higher work loads than wild-type animals. Together, these data indicate that PGC-1b drives the formation of highly oxidative fibers containing type IIX MHC.
Updated on July 12, 2020