title: The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle.
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-1alpha 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-1beta, a coactivator functionally similar to but distinct from PGC-1alpha, causes a marked induction of IIX fibers, which are oxidative but have "fast-twitch" biophysical properties. PGC-1beta coactivates the MEF2 family of transcription factors to stimulate the type IIX myosin heavy chain (MHC) promoter. PGC-1beta transgenic muscle fibers are rich in mitochondria and are highly oxidative, at least in part due to coactivation by PGC-1beta of ERRalpha and PPARalpha. Consequently, these transgenic animals can run for longer and at higher work loads than wild-type animals. Together, these data indicate that PGC-1beta drives the formation of highly oxidative fibers containing type IIX MHC.
authors.affiliation: Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Arany
authors.forename: Nathan
authors.initials: N
authors.lastname: Lebrasseur
authors.forename: Carl
authors.initials: C
authors.lastname: Morris
authors.forename: Eric
authors.initials: E
authors.lastname: Smith
authors.forename: Wenli
authors.initials: W
authors.lastname: Yang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ma
authors.forename: Sherry
authors.initials: S
authors.lastname: Chin
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D018995:Myosin Heavy Chains