TY - JOUR
T1 - The Transcriptional Coactivator PGC-1β Drives the Formation of Oxidative Type IIX Fibers in Skeletal Muscle
AU - Arany, Zoltan
AU - Lebrasseur, Nathan
AU - Morris, Carl
AU - Smith, Eric
AU - Yang, Wenli
AU - Ma, Yanhong
AU - Chin, Sherry
AU - Spiegelman, Bruce M.
N1 - Funding Information:
This work was supported by NIH grants HL079172 to Z.A. and DK54477 and DK61562 to B.M.S.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - HUMDISEASE
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U2 - 10.1016/j.cmet.2006.12.003
DO - 10.1016/j.cmet.2006.12.003
M3 - Article
C2 - 17189205
AN - SCOPUS:33845674997
SN - 1550-4131
VL - 5
SP - 35
EP - 46
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -