title: A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy.
abstract: PGC-1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise but has no effects on muscle strength or hypertrophy. We have identified a form of PGC-1α (PGC-1α4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1α4 is highly expressed in exercised muscle but does not regulate most known PGC-1α targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1α4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1α4 show increased muscle mass and strength and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1α4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a PGC-1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.
authors.affiliation: Department of Cell Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. jorge.ruas@ki.se
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Ruas
authors.forename: James P
authors.initials: JP
authors.lastname: White
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Rao
authors.forename: Sandra
authors.initials: S
authors.lastname: Kleiner
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Brannan
authors.forename: Brooke C
authors.initials: BC
authors.lastname: Harrison
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Greene
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Estall
authors.forename: Brian A
authors.initials: BA
authors.lastname: Irving
authors.forename: Ian R
authors.initials: IR
authors.lastname: Lanza
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Rasbach
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Okutsu
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Leinwand
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
mesh_terms: D050154:Adiposity; D000818:Animals; D005947:Glucose / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006984:Hypertrophy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D055435:Myostatin / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D020033:Protein Isoforms / Q000378:metabolism; D055070:Resistance Training; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D006360:Heat-Shock Proteins; D055435:Myostatin; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D020033:Protein Isoforms; D015534:Trans-Activators; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D005947:Glucose