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

8 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

Cite this

Gaur, Vidhi ; Connor, Timothy ; Venardos, Kylie ; Henstridge, Darren C. ; Martin, Sheree D ; Swinton, Courtney ; Morrison, Shona ; Aston-Mourney, Kathryn ; Gehrig, Stefan M ; van Ewijk, Roelof ; Lynch, Gordon S ; Febbraio, Mark A. ; Steinberg, Gregory R ; Hargreaves, Mark ; Walder, Ken R ; McGee, Sean L. / Scriptaid enhances skeletal muscle insulin action and cardiac function in obese mice. In: Diabetes, Obesity and Metabolism. 2017 ; Vol. 19, No. 7. pp. 936-943.
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title = "Scriptaid enhances skeletal muscle insulin action and cardiac function in obese mice",
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.",
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author = "Vidhi Gaur and Timothy Connor and Kylie Venardos and Henstridge, {Darren C.} and Martin, {Sheree D} and Courtney Swinton and Shona Morrison and Kathryn Aston-Mourney and Gehrig, {Stefan M} and {van Ewijk}, Roelof and Lynch, {Gordon S} and Febbraio, {Mark A.} and Steinberg, {Gregory R} and Mark Hargreaves and Walder, {Ken R} and McGee, {Sean L}",
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Gaur, V, Connor, T, Venardos, K, Henstridge, DC, Martin, SD, Swinton, C, Morrison, S, Aston-Mourney, K, Gehrig, SM, van Ewijk, R, Lynch, GS, Febbraio, MA, Steinberg, GR, Hargreaves, M, Walder, KR & 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. https://doi.org/10.1111/dom.12896

Scriptaid enhances skeletal muscle insulin action and cardiac function in obese mice. / Gaur, Vidhi; Connor, Timothy; Venardos, Kylie; Henstridge, Darren C.; Martin, Sheree D; Swinton, Courtney; Morrison, Shona; Aston-Mourney, Kathryn; Gehrig, Stefan M; van Ewijk, Roelof; Lynch, Gordon S; Febbraio, Mark A.; Steinberg, Gregory R; Hargreaves, Mark; Walder, Ken R; McGee, Sean L.

In: Diabetes, Obesity and Metabolism, Vol. 19, No. 7, 01.07.2017, p. 936-943.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Scriptaid enhances skeletal muscle insulin action and cardiac function in obese mice

AU - Gaur, Vidhi

AU - Connor, Timothy

AU - Venardos, Kylie

AU - Henstridge, Darren C.

AU - Martin, Sheree D

AU - Swinton, Courtney

AU - Morrison, Shona

AU - Aston-Mourney, Kathryn

AU - Gehrig, Stefan M

AU - van Ewijk, Roelof

AU - Lynch, Gordon S

AU - Febbraio, Mark A.

AU - Steinberg, Gregory R

AU - Hargreaves, Mark

AU - Walder, Ken R

AU - McGee, Sean L

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

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KW - animal pharmacology

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U2 - 10.1111/dom.12896

DO - 10.1111/dom.12896

M3 - Article

VL - 19

SP - 936

EP - 943

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1463-1326

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