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

Alessandra Ferrari, Raffaella Longo, Erika Fiorino, Rui Silva, Nico Mitro, Gaia Cermenati, Federica Gilardi, Béatrice Desvergne, Annapaola Andolfo, Cinzia Magagnotti, Donatella Caruso, Emma De Fabiani, Scott W. Hiebert and Maurizio Crestani ()
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Alessandra Ferrari: Università degli Studi di Milano
Raffaella Longo: Università degli Studi di Milano
Erika Fiorino: Università degli Studi di Milano
Rui Silva: Università degli Studi di Milano
Nico Mitro: Università degli Studi di Milano
Gaia Cermenati: Università degli Studi di Milano
Federica Gilardi: Université de Lausanne
Béatrice Desvergne: Université de Lausanne
Annapaola Andolfo: San Raffaele Scientific Institute
Cinzia Magagnotti: San Raffaele Scientific Institute
Donatella Caruso: Università degli Studi di Milano
Emma De Fabiani: Università degli Studi di Milano
Scott W. Hiebert: Vanderbilt University School of Medicine
Maurizio Crestani: Università degli Studi di Milano

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00182-7

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