Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice
- École Normale Supérieure de Lyon, France
- Inserm, France
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
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Target genes of thyroid hormone (TH) in brown adipose tissue (BAT) and their role during metabolic stressorsNCBI Gene Expression Omnibus, GSE201136.
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A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissueNCBI Gene Expression Omnibus, GSE110053.
Article and author information
Author details
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.
Reviewing Editor
- Rauf Latif, Icahn School of Medicine at Mount Sinai, United States
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.
Version history
- Received: July 19, 2022
- Preprint posted: August 6, 2022 (view preprint)
- Accepted: November 11, 2022
- Accepted Manuscript published: November 14, 2022 (version 1)
- 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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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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