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

Author

Listed:
  • Alessandra Ferrari

    (Università degli Studi di Milano
    University of California Los Angeles)

  • 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)

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.

Suggested Citation

  • Alessandra Ferrari & Raffaella Longo & Erika Fiorino & Rui Silva & Nico Mitro & Gaia Cermenati & Federica Gilardi & Béatrice Desvergne & Annapaola Andolfo & Cinzia Magagnotti & Donatella Caruso & Emma, 2017. "HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00182-7
    DOI: 10.1038/s41467-017-00182-7
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