title: NCoR1 is a conserved physiological modulator of muscle mass and oxidative function.
abstract: Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARβ/δ, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function.
authors.affiliation: Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Evan G
authors.initials: EG
authors.lastname: Williams
authors.forename: Laurent
authors.initials: L
authors.lastname: Mouchiroud
authors.forename: Carles
authors.initials: C
authors.lastname: Cantó
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.forename: Michael
authors.initials: M
authors.lastname: Downes
authors.forename: Christophe
authors.initials: C
authors.lastname: Héligon
authors.forename: Grant D
authors.initials: GD
authors.lastname: Barish
authors.forename: Béatrice
authors.initials: B
authors.lastname: Desvergne
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008931:Mitochondria, Muscle / Q000378:metabolism; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics / Q000378:metabolism*; D047494:PPAR delta / Q000378:metabolism; D048068:PPAR-beta / Q000378:metabolism; D010805:Physical Conditioning, Animal
chemical_list: D029742:Caenorhabditis elegans Proteins; C539128:Ncor1 protein, mouse; D056971:Nuclear Receptor Co-Repressor 1; D047494:PPAR delta; D048068:PPAR-beta
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