Scriptaid enhances skeletal muscle insulin action and cardiac function in obese mice

Vidhi Gaur, Timothy Connor, Kylie Venardos, Darren C. Henstridge, Sheree D Martin, Courtney Swinton, Shona Morrison, Kathryn Aston-Mourney, Stefan M Gehrig, Roelof van Ewijk, Gordon S Lynch, Mark A. Febbraio, Gregory R Steinberg, Mark Hargreaves, Ken R Walder, Sean L McGee

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

Aim: To determine the effect of Scriptaid, a compound that can replicate aspects of the exercise adaptive response through disruption of the class IIa histone deacetylase (HDAC) corepressor complex, on muscle insulin action in obesity. Materials and methods: Diet-induced obese mice were administered Scriptaid (1 mg/kg) via daily intraperitoneal injection for 4 weeks. Whole-body and skeletal muscle metabolic phenotyping of mice was performed, in addition to echocardiography, to assess cardiac morphology and function. Results: Scriptaid treatment had no effect on body weight or composition, but did increase energy expenditure, supported by increased lipid oxidation, while food intake was also increased. Scriptaid enhanced the expression of oxidative genes and proteins, increased fatty acid oxidation and reduced triglycerides and diacylglycerides in skeletal muscle. Furthermore, ex vivo insulin-stimulated glucose uptake by skeletal muscle was enhanced. Surprisingly, heart weight was reduced in Scriptaid-treated mice and was associated with enhanced expression of genes involved in oxidative metabolism in the heart. Scriptaid also improved indices of both diastolic and systolic cardiac function. Conclusion: These data show that pharmacological targeting of the class IIa HDAC corepressor complex with Scriptaid could be used to enhance muscle insulin action and cardiac function in obesity.

Original languageEnglish
Pages (from-to)936-943
Number of pages8
JournalDiabetes, Obesity and Metabolism
Volume19
Issue number7
DOIs
Publication statusPublished - 1 Jul 2017
Externally publishedYes

Keywords

  • animal pharmacology

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