University of Tasmania
133362 - Disruption of the class IIa HDAC corepressor complex increases energy expenditure and lipid oxidation.pdf (2.75 MB)

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

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journal contribution
posted on 2023-05-20, 04:46 authored by Gaur, V, Connor, T, Sanigorski, A, Martin, SD, Bruce, CR, Darren HenstridgeDarren Henstridge, Bond, ST, McEwen, KA, Kerr-Bayles, L, Ashton, TD, Fleming, C, Wu, M, Pike Winer, LS, Chen, D, Hudson, GM, Schwabe, JWR, Baar, K, Febbraio, MA, Gregorevic, P, Pfeffer, FM, Walder, KR, Hargreaves, M, McGee, SL
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.


Publication title

Cell Reports










School of Health Sciences


Elsevier Inc.

Place of publication

United States

Rights statement

Copyright 2016 the authors. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified