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Title: Disruption of the Class IIa HDAC Corepressor Complex Increases Energy Expenditure and Lipid Oxidation
Authors: Gaur, V.
Connor, T.
Sanigorski, A.
Martin, S. D.
Bruce, C. R.
Henstridge, D. C.
Bond, S. T.
McEwen, K. A.
Kerr-Bayles, L.
Ashton, T. D.
Fleming, C.
Wu, M.
Winer, L. S. P.
Chen, D.
Hudson, Gregg M.
Schwabe, John W. R.
Baar, K.
Febbraio, M. A.
Gregorevic, P.
Pfeffer, F. M.
Walder, K. R.
Hargreaves, M.
McGee, S. L.
First Published: 13-Sep-2016
Publisher: Elsevier (Cell Press): OAJ
Citation: Cell Reports, 2016, 16 (11), pp. 2802-2810 (9)
Abstract: Drugs that recapitulate aspects of the exercise adaptive response have the potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase) transcriptional repressive activity during exercise. Here, we find that exercise-like adaptations are induced by skeletal muscle expression of class IIa HDAC mutants that cannot form a corepressor complex. Adaptations include increased metabolic gene expression, mitochondrial capacity, and lipid oxidation. An existing HDAC inhibitor, Scriptaid, had similar phenotypic effects through disruption of the class IIa HDAC corepressor complex. Acute Scriptaid administration to mice increased the expression of metabolic genes, which required an intact class IIa HDAC corepressor complex. Chronic Scriptaid administration increased exercise capacity, whole-body energy expenditure and lipid oxidation, and reduced fasting blood lipids and glucose. Therefore, compounds that disrupt class IIa HDAC function could be used to enhance metabolic health in chronic diseases driven by physical inactivity.
DOI Link: 10.1016/j.celrep.2016.08.005
ISSN: 2211-1247
eISSN: 2211-1247
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: This is an open access article under the CC BY-NC-ND license (
Description: The accession number for the microarray dataset reported in this paper is GEO: GSE54642.
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology

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