Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice

Abstract

Thyroid hormone (T3) and its nuclear receptors (TR) are important regulators of energy expenditure and adaptive thermogenesis, notably through their action in the brown adipose tissue (BAT). However, T3 acts in many other peripheral and central tissues which are also involved in energy expenditure. The general picture of how T3 regulates BAT thermogenesis is currently not fully established, notably due to the absence of extensive omics analyses and the lack of specific mice model. Here, we first used transcriptome and cistrome analyses to establish the list of T3/TR direct target genes in brown adipocytes. We then developed a novel model of transgenic mice, in which T3 signaling is specifically suppressed in brown adipocytes at adult stage. We addressed the capacity of these mice to mount a thermogenic response when challenged by either a cold exposure or a high-fat diet, and analyzed the associated changes in BAT transcriptome. We conclude that T3 plays a crucial role in the thermogenic response of the BAT, controlling the expression of genes involved in lipid and glucose metabolism and regulating BAT proliferation. The resulting picture provides an unprecedented view on the pathways by which T3 activates energy expenditure through an efficient adaptive thermogenesis in the BAT.

Data availability

The raw sequencing data and aligned read counts generated as part of this study has been deposited to the NCBI Sequence Read Archive. Accession number: GSE201136; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE201136

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Yanis Zekri

    Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, Lyon, France
    For correspondence
    yanis.zekri@ens-lyon.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4925-4610
  2. Romain Guyot

    Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Inés Garteizgogeascoa Suñer

    Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Laurence Canaple

    Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Amandine Gautier Stein

    Inserm, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Justine Vily Petit

    Inserm, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Denise Aubert

    Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Sabine Richard

    Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Frederic Flamant

    Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3360-2345
  10. Karine Gauthier

    Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.

Funding

European Union's Horizon 2020 (825753)

  • Frederic Flamant

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were carried out in accordance with the European Community Council Directive of September 22, 2010 (2010/63/EU) regarding the protection of animals used for experimental and other scientific purposes. The research project was approved by a local animal care and use committee (C2EA015) and authorized by the French Ministry of Research.

Reviewing Editor

  1. Rauf Latif, Icahn School of Medicine at Mount Sinai, United States

Publication history

  1. Received: July 19, 2022
  2. Preprint posted: August 6, 2022 (view preprint)
  3. Accepted: November 11, 2022
  4. Accepted Manuscript published: November 14, 2022 (version 1)
  5. Version of Record published: November 23, 2022 (version 2)

Copyright

© 2022, Zekri et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yanis Zekri
  2. Romain Guyot
  3. Inés Garteizgogeascoa Suñer
  4. Laurence Canaple
  5. Amandine Gautier Stein
  6. Justine Vily Petit
  7. Denise Aubert
  8. Sabine Richard
  9. Frederic Flamant
  10. Karine Gauthier
(2022)
Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice
eLife 11:e81996.
https://doi.org/10.7554/eLife.81996

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