TY - JOUR
T1 - NCoR1 is a conserved physiological modulator of muscle mass and oxidative function
AU - Yamamoto, Hiroyasu
AU - Williams, Evan G.
AU - Mouchiroud, Laurent
AU - Cantó, Carles
AU - Fan, Weiwei
AU - Downes, Michael
AU - Héligon, Christophe
AU - Barish, Grant D.
AU - Desvergne, Béatrice
AU - Evans, Ronald M.
AU - Schoonjans, Kristina
AU - Auwerx, Johan
N1 - Funding Information:
We acknowledge M. Lazar (University of Pennsylvania, Philadelphia), A. Kralli (Scripps Research Institute, San Diego), J.-S. Annicotte and L. Fajas (Institut de Génétique Moléculaire de Montpellier, France), A. Lusis (University of California, Los Angeles), K. Schughart (Helmholtz Zentrum, Hannover, Germany), R. Williams (University of Tennessee Health Science Center, Memphis), and the Caenorhabditis Genetics Center (CGC) for generous sharing of research reagents and data. We thank N. Messadeq (Institut Clinique de la Souris, Strasbourg, France) for EM analysis and the Center for PhenoGenomics (CPG) at the EPFL for help with mouse phenotyping. This work was supported by the École Polytechnique Fédérale de Lausanne, Swiss National Science Foundation, NIH (DK059820 to J.A., DK062434 to R.M.E., 1K08HL092298 to G.D.B., HD027183 to R.M.E., and DK057978 to R.M.E.), the EU ideas program (ERC-2008-AdG-23118), the Helmsley Charitable Trust, the Glenn Foundation, and the Howard Hughes Medical Institute (HHMI). H.Y. was supported by an FRM fellowship. R.M.E. is an Investigator of the HHMI and the March of Dimes Chair in Molecular and Developmental Biology. J.A. is the Nestle Chair in Energy Metabolism. We thank the members of the Auwerx lab and R. Williams for discussions.
PY - 2011/11/11
Y1 - 2011/11/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=81055125669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81055125669&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2011.10.017
DO - 10.1016/j.cell.2011.10.017
M3 - Article
C2 - 22078881
AN - SCOPUS:81055125669
VL - 147
SP - 827
EP - 839
JO - Cell
JF - Cell
SN - 0092-8674
IS - 4
ER -