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

Gaur, Vidhi, Connor, Timothy, Sanigorski, Andrew, Martin, Sheree D., Bruce, Clinton R., Henstridge, Darren C., Bond, Simon T., McEwen, Kevin A., Kerr-Bayles, Lyndal, Ashton, Trent D., Fleming, Cassandra, Wu, Min, Pike Winer, Lisa S., Chen, Denise, Hudson, Gregg M., Schwabe, John W.R., Baar, Keith, Febbraio, Mark A., Gregorevic, Paul, Pfeffer, Frederick M., Walder, Ken R., Hargreaves, Mark and McGee, Sean L. 2016, Disruption of the class IIa HDAC corepressor complex increases energy expenditure and lipid oxidation, Cell reports, vol. 16, no. 11, pp. 2802-2810, doi: 10.1016/j.celrep.2016.08.005.

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Title Disruption of the class IIa HDAC corepressor complex increases energy expenditure and lipid oxidation
Author(s) Gaur, Vidhi
Connor, Timothy
Sanigorski, AndrewORCID iD for Sanigorski, Andrew orcid.org/0000-0002-2858-4621
Martin, Sheree D.
Bruce, Clinton R.ORCID iD for Bruce, Clinton R. orcid.org/0000-0002-0515-3343
Henstridge, Darren C.
Bond, Simon T.
McEwen, Kevin A.
Kerr-Bayles, Lyndal
Ashton, Trent D.ORCID iD for Ashton, Trent D. orcid.org/0000-0002-6707-6064
Fleming, Cassandra
Wu, Min
Pike Winer, Lisa S.
Chen, Denise
Hudson, Gregg M.
Schwabe, John W.R.
Baar, Keith
Febbraio, Mark A.
Gregorevic, Paul
Pfeffer, Frederick M.
Walder, Ken R.ORCID iD for Walder, Ken R. orcid.org/0000-0002-6758-4763
Hargreaves, Mark
McGee, Sean L.ORCID iD for McGee, Sean L. orcid.org/0000-0001-6953-106X
Journal name Cell reports
Volume number 16
Issue number 11
Start page 2802
End page 2810
Total pages 9
Publisher Elsevier
Place of publication New York, N.Y.
Publication date 2016-09-13
ISSN 2211-1247
Keyword(s) HDAC4
skeletal muscle
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Summary 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.
Language eng
DOI 10.1016/j.celrep.2016.08.005
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Persistent URL http://hdl.handle.net/10536/DRO/DU:30086375

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