Disruption of the Class IIa HDAC Corepressor Complex Increases Energy Expenditure and Lipid Oxidation

作者：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; Winer Lisa S Pike; Chen Denise; Hudson Gregg M; Schwabe John W R; Baar Keith; Febbraio Mark A; Gregorevic Paul; Pfeffer Frederick M; Walder Ken R; Hargreaves Mark; McGee Sean L^*

来源：Cell Reports, 2016, 16(11): 2802-2810.

DOI：10.1016/j.celrep.2016.08.005

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.

• 出版日期2016-9-13
• 单位迪肯大学; 河北医科大学