HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning.

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Serval ID
serval:BIB_910F88CBC37F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning.
Journal
Nature Communications
Author(s)
Ferrari A., Longo R., Fiorino E., Silva R., Mitro N., Cermenati G., Gilardi F., Desvergne B., Andolfo A., Magagnotti C., Caruso D., Fabiani E., Hiebert S.W., Crestani M.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
8
Number
1
Pages
93
Language
english
Abstract
White adipose tissue (WAT) can undergo a phenotypic switch, known as browning, in response to environmental stimuli such as cold. Post-translational modifications of histones have been shown to regulate cellular energy metabolism, but their role in white adipose tissue physiology remains incompletely understood. Here we show that histone deacetylase 3 (HDAC3) regulates WAT metabolism and function. Selective ablation of Hdac3 in fat switches the metabolic signature of WAT by activating a futile cycle of de novo fatty acid synthesis and β-oxidation that potentiates WAT oxidative capacity and ultimately supports browning. Specific ablation of Hdac3 in adipose tissue increases acetylation of enhancers in Pparg and Ucp1 genes, and of putative regulatory regions of the Ppara gene. Our results unveil HDAC3 as a regulator of WAT physiology, which acts as a molecular brake that inhibits fatty acid metabolism and WAT browning.Histone deacetylases, such as HDAC3, have been shown to alter cellular metabolism in various tissues. Here the authors show that HDAC3 regulates WAT metabolism by activating a futile cycle of fatty acid synthesis and oxidation, which supports WAT browning.

Keywords
Adipocytes/physiology, Adipose Tissue, Brown/physiology, Adipose Tissue, White/physiology, Animals, Cell Line, Diet, High-Fat, Gene Expression Regulation/physiology, Gene Silencing, Histone Deacetylases/genetics, Histone Deacetylases/metabolism, Lipid Metabolism, Male, Mice, Mice, Knockout
Pubmed
Web of science
Open Access
Yes
Create date
28/08/2017 11:17
Last modification date
20/08/2019 15:54
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