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Disruption of the class IIa HDAC corepressor complex increases energy expenditure and lipid oxidation

Citation

Gaur, V and Connor, T and Sanigorski, A and Martin, SD and Bruce, CR and Henstridge, DC and Bond, ST and McEwen, KA and Kerr-Bayles, L and Ashton, TD and Fleming, C and Wu, M and Pike Winer, LS and Chen, D and Hudson, GM and Schwabe, JWR and Baar, K and Febbraio, MA and Gregorevic, P and Pfeffer, FM and Walder, KR and Hargreaves, M and McGee, SL, Disruption of the class IIa HDAC corepressor complex increases energy expenditure and lipid oxidation, Cell Reports, 16, (11) pp. 2802-2810. ISSN 2211-1247 (2016) [Refereed Article]


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Copyright 2016 the authors. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/

DOI: doi:10.1016/j.celrep.2016.08.005

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.

Item Details

Item Type:Refereed Article
Keywords:HDAC4, HDAC5, MEF2, skeletal muscle, 6 (1,3 dioxo 1h,3h benzo[de]isoquinolin 2 yl) n hydroxyhexanamide, corepressor protein, glucose, histone deacetylase 2, lipid, corepressor protein, Hdac5 protein, mouse, histone deacetylase, hydroxylamine, male
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133362
Year Published:2016
Web of Science® Times Cited:40
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-22
Downloads:8 View Download Statistics

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