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Class I and II Histone Deacetylase Inhibitors Differentially Regulate Thermogenic Gene Expression in Brown Adipocytes
Class I histone deacetylase inhibitors (HDACis) enhance whole body energy expenditure and attenuate high fat diet-induced insulin resistance. However, it is not clear whether this is exerted directly through activating brown fat thermogenesis. Here, we find that pan-HDACi TSA exerts paradoxical effe...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117331/ https://www.ncbi.nlm.nih.gov/pubmed/30166563 http://dx.doi.org/10.1038/s41598-018-31560-w |
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author | Rajan, Anubama Shi, Hang Xue, Bingzhong |
author_facet | Rajan, Anubama Shi, Hang Xue, Bingzhong |
author_sort | Rajan, Anubama |
collection | PubMed |
description | Class I histone deacetylase inhibitors (HDACis) enhance whole body energy expenditure and attenuate high fat diet-induced insulin resistance. However, it is not clear whether this is exerted directly through activating brown fat thermogenesis. Here, we find that pan-HDACi TSA exerts paradoxical effects on brown fat gene expression, as it inhibits the expression of Ucp1, Pparγ and Prdm16 in brown adipocytes, while promoting the expression of other brown fat-specific genes such as Pgc1α, Pgc1β, Acox1 and Cidea. Further studies indicate that class I HDACi MS-275 significantly increases; whereas class II HDACi MC-1568 markedly reduces, the expression of Ucp1 and other brown fat-specific genes in treated brown adipocytes. ChIP assay reveals an enhanced H3 acetylation at the Pgc1α promoter in MS-275-treated brown adipocytes; whereas the effect of MC-1568 is associated with up-regulation of retinoblastoma protein (Rb) and an enhanced acetylation of H3K27 at the Rb promoter. Loss of function studies indicate that Pgc1α up-regulation largely mediates the stimulatory effect of class I HDACis on the thermogenic program, whereas up-regulation of Rb may be responsible for the inhibitory effect of class II HDACis. Thus, our data suggest that class I and II HDACis have differential effects on brown fat thermogenic gene expression. |
format | Online Article Text |
id | pubmed-6117331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61173312018-09-05 Class I and II Histone Deacetylase Inhibitors Differentially Regulate Thermogenic Gene Expression in Brown Adipocytes Rajan, Anubama Shi, Hang Xue, Bingzhong Sci Rep Article Class I histone deacetylase inhibitors (HDACis) enhance whole body energy expenditure and attenuate high fat diet-induced insulin resistance. However, it is not clear whether this is exerted directly through activating brown fat thermogenesis. Here, we find that pan-HDACi TSA exerts paradoxical effects on brown fat gene expression, as it inhibits the expression of Ucp1, Pparγ and Prdm16 in brown adipocytes, while promoting the expression of other brown fat-specific genes such as Pgc1α, Pgc1β, Acox1 and Cidea. Further studies indicate that class I HDACi MS-275 significantly increases; whereas class II HDACi MC-1568 markedly reduces, the expression of Ucp1 and other brown fat-specific genes in treated brown adipocytes. ChIP assay reveals an enhanced H3 acetylation at the Pgc1α promoter in MS-275-treated brown adipocytes; whereas the effect of MC-1568 is associated with up-regulation of retinoblastoma protein (Rb) and an enhanced acetylation of H3K27 at the Rb promoter. Loss of function studies indicate that Pgc1α up-regulation largely mediates the stimulatory effect of class I HDACis on the thermogenic program, whereas up-regulation of Rb may be responsible for the inhibitory effect of class II HDACis. Thus, our data suggest that class I and II HDACis have differential effects on brown fat thermogenic gene expression. Nature Publishing Group UK 2018-08-30 /pmc/articles/PMC6117331/ /pubmed/30166563 http://dx.doi.org/10.1038/s41598-018-31560-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Rajan, Anubama Shi, Hang Xue, Bingzhong Class I and II Histone Deacetylase Inhibitors Differentially Regulate Thermogenic Gene Expression in Brown Adipocytes |
title | Class I and II Histone Deacetylase Inhibitors Differentially Regulate Thermogenic Gene Expression in Brown Adipocytes |
title_full | Class I and II Histone Deacetylase Inhibitors Differentially Regulate Thermogenic Gene Expression in Brown Adipocytes |
title_fullStr | Class I and II Histone Deacetylase Inhibitors Differentially Regulate Thermogenic Gene Expression in Brown Adipocytes |
title_full_unstemmed | Class I and II Histone Deacetylase Inhibitors Differentially Regulate Thermogenic Gene Expression in Brown Adipocytes |
title_short | Class I and II Histone Deacetylase Inhibitors Differentially Regulate Thermogenic Gene Expression in Brown Adipocytes |
title_sort | class i and ii histone deacetylase inhibitors differentially regulate thermogenic gene expression in brown adipocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117331/ https://www.ncbi.nlm.nih.gov/pubmed/30166563 http://dx.doi.org/10.1038/s41598-018-31560-w |
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