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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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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. |
format | Online Article Text |
id | pubmed-3581211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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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