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

Gaur, V, Connor, T, Venardos, K, Henstridge, DC ORCID: 0000-0003-4988-767X, Martin, SD, Swinton, C, Morrison, S, Aston-Mourney, K, Gehrig, SM, van Ewijk, R, Lynch, GS, Febbraio, MA, Steinberg, GR, Hargreaves, M, Walder, KR and McGee, SL 2017 , 'Scriptaid enhances skeletal muscle insulin action and cardiac function in obese mice' , Diabetes, Obesity and Metabolism, vol. 19, no. 7 , pp. 936-943 , doi: 10.1111/dom.12896.

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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.

Item Type: Article
Authors/Creators:Gaur, V and Connor, T and Venardos, K and Henstridge, DC and Martin, SD and Swinton, C and Morrison, S and Aston-Mourney, K and Gehrig, SM and van Ewijk, R and Lynch, GS and Febbraio, MA and Steinberg, GR and Hargreaves, M and Walder, KR and McGee, SL
Keywords: animal pharmacology, 6 (1,3 dioxo 1h,3h benzo[de]isoquinolin 2 yl) n hydroxyhexanamide, diacylglycerol, histone deacetylase, insulin, triacylglycerol, antiobesity agent, animal model
Journal or Publication Title: Diabetes, Obesity and Metabolism
Publisher: Blackwell Publishing Ltd
ISSN: 1462-8902
DOI / ID Number: 10.1111/dom.12896
Copyright Information:

Copyright 2017 John Wiley & Sons Ltd.

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