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Scriptaid enhances skeletal muscle insulin action and cardiac function in obese mice
Author(s) -
Gaur Vidhi,
Connor Timothy,
Venardos Kylie,
Henstridge Darren C.,
Martin Sheree D.,
Swinton Courtney,
Morrison Shona,
AstonMourney Kathryn,
Gehrig Stefan M.,
van Ewijk Roelof,
Lynch Gordon S.,
Febbraio Mark A.,
Steinberg Gregory R.,
Hargreaves Mark,
Walder Ken R.,
McGee Sean L.
Publication year - 2017
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12896
Subject(s) - skeletal muscle , endocrinology , medicine , corepressor , insulin , cardiac function curve , cardiac muscle , glucose uptake , beta oxidation , in vivo , metabolism , biology , gene expression , heart failure , biochemistry , gene , psychological repression , microbiology and biotechnology
Aim To determine the effect of S criptaid, 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 S criptaid (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. S criptaid 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 S criptaid could be used to enhance muscle insulin action and cardiac function in obesity.