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

Z Arany, N Lebrasseur, C Morris, E Smith, W Yang… - Cell metabolism, 2007 - cell.com
Z Arany, N Lebrasseur, C Morris, E Smith, W Yang, Y Ma, S Chin, BM Spiegelman
Cell metabolism, 2007cell.com
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 …
Summary
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.
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