Journal article
Disruption of the Class IIa HDAC Corepressor Complex Increases Energy Expenditure and Lipid Oxidation
V Gaur, T Connor, A Sanigorski, SD Martin, CR Bruce, DC Henstridge, ST Bond, KA McEwen, L Kerr-Bayles, TD Ashton, C Fleming, M Wu, LS Pike Winer, D Chen, GM Hudson, JWR Schwabe, K Baar, MA Febbraio, P Gregorevic, FM Pfeffer Show all
Cell Reports | CELL PRESS | Published : 2016
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 Scripta..
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Awarded by Wellcome Trust
Funding Acknowledgements
The authors wish to thank Assoc. Prof. Peter Meikle (Metabolomics Laboratory, Baker IDI) for assistance with lipid analysis, Hongwei Qian for AAV production, and Alex Nelson for technical assistance. This research was supported by the Diabetes Australia Research Trust Viertel Award and by grants from the National Health and Medical Research Council (NHMRC) of Australia (1027727) and the Deakin University Molecular and Medical Research Strategic Research Centre to S.L.M. J.W.R.S. is supported by Wellcome Trust Senior Investigator Award WT100237 and is a Royal Society Merit Award Holder. M.A.F., P.G., and S.L.M. are supported by research fellowships from the NHMRC.