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.
HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning / A. Ferrari, R. Longo, E. Fiorino, R.G. Teixeira da Silva, N. Mitro, G. Cermenati, F. Gilardi, D. Béatrice, A. Annapaola, M. Cinzia, D. Caruso, E. De Fabiani, H. Scott W., M. Crestani. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 8:1(2017 Jul 21).
|Titolo:||HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning|
CRESTANI, MAURIZIO (Corresponding)
|Parole Chiave:||adipocytes; adipose tissue, brown; adipose tissue, white; animals; cell line; diet, high-fat; gene expression regulation; gene silencing; histone deacetylases; lipid metabolism; male; mice; mice, knockout; chemistry (all); biochemistry, genetics and molecular biology (all)|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Progetto:||Histone deacetylase 3 in adipose tissue: a link between immuno-metabolic dysfunctions and obesity and type 2 diabetes|
Control of metabolic and inflammatory pathways by nuclear receptor
|Data di pubblicazione:||21-lug-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/s41467-017-00182-7|
|Appare nelle tipologie:||01 - Articolo su periodico|