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Inhibition of Class I Histone Deacetylases Unveils a Mitochondrial Signature and Enhances Oxidative Metabolism in Skeletal Muscle and Adipose Tissue

Chromatin modifications are sensitive to environmental and nutritional stimuli. Abnormalities in epigenetic regulation are associated with metabolic disorders such as obesity and diabetes that are often linked with defects in oxidative metabolism. Here, we evaluated the potential of class-specific s...

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Autores principales: Galmozzi, Andrea, Mitro, Nico, Ferrari, Alessandra, Gers, Elise, Gilardi, Federica, Godio, Cristina, Cermenati, Gaia, Gualerzi, Alice, Donetti, Elena, Rotili, Dante, Valente, Sergio, Guerrini, Uliano, Caruso, Donatella, Mai, Antonello, Saez, Enrique, De Fabiani, Emma, Crestani, Maurizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581211/
https://www.ncbi.nlm.nih.gov/pubmed/23069623
http://dx.doi.org/10.2337/db12-0548
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author Galmozzi, Andrea
Mitro, Nico
Ferrari, Alessandra
Gers, Elise
Gilardi, Federica
Godio, Cristina
Cermenati, Gaia
Gualerzi, Alice
Donetti, Elena
Rotili, Dante
Valente, Sergio
Guerrini, Uliano
Caruso, Donatella
Mai, Antonello
Saez, Enrique
De Fabiani, Emma
Crestani, Maurizio
author_facet Galmozzi, Andrea
Mitro, Nico
Ferrari, Alessandra
Gers, Elise
Gilardi, Federica
Godio, Cristina
Cermenati, Gaia
Gualerzi, Alice
Donetti, Elena
Rotili, Dante
Valente, Sergio
Guerrini, Uliano
Caruso, Donatella
Mai, Antonello
Saez, Enrique
De Fabiani, Emma
Crestani, Maurizio
author_sort Galmozzi, Andrea
collection PubMed
description Chromatin modifications are sensitive to environmental and nutritional stimuli. Abnormalities in epigenetic regulation are associated with metabolic disorders such as obesity and diabetes that are often linked with defects in oxidative metabolism. Here, we evaluated the potential of class-specific synthetic inhibitors of histone deacetylases (HDACs), central chromatin-remodeling enzymes, to ameliorate metabolic dysfunction. Cultured myotubes and primary brown adipocytes treated with a class I–specific HDAC inhibitor showed higher expression of Pgc-1α, increased mitochondrial biogenesis, and augmented oxygen consumption. Treatment of obese diabetic mice with a class I– but not a class II–selective HDAC inhibitor enhanced oxidative metabolism in skeletal muscle and adipose tissue and promoted energy expenditure, thus reducing body weight and glucose and insulin levels. These effects can be ascribed to increased Pgc-1α action in skeletal muscle and enhanced PPARγ/PGC-1α signaling in adipose tissue. In vivo ChIP experiments indicated that inhibition of HDAC3 may account for the beneficial effect of the class I–selective HDAC inhibitor. These results suggest that class I HDAC inhibitors may provide a pharmacologic approach to treating type 2 diabetes.
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spelling pubmed-35812112014-03-01 Inhibition of Class I Histone Deacetylases Unveils a Mitochondrial Signature and Enhances Oxidative Metabolism in Skeletal Muscle and Adipose Tissue Galmozzi, Andrea Mitro, Nico Ferrari, Alessandra Gers, Elise Gilardi, Federica Godio, Cristina Cermenati, Gaia Gualerzi, Alice Donetti, Elena Rotili, Dante Valente, Sergio Guerrini, Uliano Caruso, Donatella Mai, Antonello Saez, Enrique De Fabiani, Emma Crestani, Maurizio Diabetes Metabolism Chromatin modifications are sensitive to environmental and nutritional stimuli. Abnormalities in epigenetic regulation are associated with metabolic disorders such as obesity and diabetes that are often linked with defects in oxidative metabolism. Here, we evaluated the potential of class-specific synthetic inhibitors of histone deacetylases (HDACs), central chromatin-remodeling enzymes, to ameliorate metabolic dysfunction. Cultured myotubes and primary brown adipocytes treated with a class I–specific HDAC inhibitor showed higher expression of Pgc-1α, increased mitochondrial biogenesis, and augmented oxygen consumption. Treatment of obese diabetic mice with a class I– but not a class II–selective HDAC inhibitor enhanced oxidative metabolism in skeletal muscle and adipose tissue and promoted energy expenditure, thus reducing body weight and glucose and insulin levels. These effects can be ascribed to increased Pgc-1α action in skeletal muscle and enhanced PPARγ/PGC-1α signaling in adipose tissue. In vivo ChIP experiments indicated that inhibition of HDAC3 may account for the beneficial effect of the class I–selective HDAC inhibitor. These results suggest that class I HDAC inhibitors may provide a pharmacologic approach to treating type 2 diabetes. American Diabetes Association 2013-03 2013-02-14 /pmc/articles/PMC3581211/ /pubmed/23069623 http://dx.doi.org/10.2337/db12-0548 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Metabolism
Galmozzi, Andrea
Mitro, Nico
Ferrari, Alessandra
Gers, Elise
Gilardi, Federica
Godio, Cristina
Cermenati, Gaia
Gualerzi, Alice
Donetti, Elena
Rotili, Dante
Valente, Sergio
Guerrini, Uliano
Caruso, Donatella
Mai, Antonello
Saez, Enrique
De Fabiani, Emma
Crestani, Maurizio
Inhibition of Class I Histone Deacetylases Unveils a Mitochondrial Signature and Enhances Oxidative Metabolism in Skeletal Muscle and Adipose Tissue
title Inhibition of Class I Histone Deacetylases Unveils a Mitochondrial Signature and Enhances Oxidative Metabolism in Skeletal Muscle and Adipose Tissue
title_full Inhibition of Class I Histone Deacetylases Unveils a Mitochondrial Signature and Enhances Oxidative Metabolism in Skeletal Muscle and Adipose Tissue
title_fullStr Inhibition of Class I Histone Deacetylases Unveils a Mitochondrial Signature and Enhances Oxidative Metabolism in Skeletal Muscle and Adipose Tissue
title_full_unstemmed Inhibition of Class I Histone Deacetylases Unveils a Mitochondrial Signature and Enhances Oxidative Metabolism in Skeletal Muscle and Adipose Tissue
title_short Inhibition of Class I Histone Deacetylases Unveils a Mitochondrial Signature and Enhances Oxidative Metabolism in Skeletal Muscle and Adipose Tissue
title_sort inhibition of class i histone deacetylases unveils a mitochondrial signature and enhances oxidative metabolism in skeletal muscle and adipose tissue
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581211/
https://www.ncbi.nlm.nih.gov/pubmed/23069623
http://dx.doi.org/10.2337/db12-0548
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