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The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes

Forkhead box transcription factors have been shown to be involved in various developmental and differentiation processes. In particular, members of the FoxP family have been previously characterized in depth for their participation in the regulation of lung and neuronal cell differentiation and T-ce...

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Autores principales: Perie, Luce, Verma, Narendra, Mueller, Elisabetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411233/
https://www.ncbi.nlm.nih.gov/pubmed/34384787
http://dx.doi.org/10.1016/j.jlr.2021.100102
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author Perie, Luce
Verma, Narendra
Mueller, Elisabetta
author_facet Perie, Luce
Verma, Narendra
Mueller, Elisabetta
author_sort Perie, Luce
collection PubMed
description Forkhead box transcription factors have been shown to be involved in various developmental and differentiation processes. In particular, members of the FoxP family have been previously characterized in depth for their participation in the regulation of lung and neuronal cell differentiation and T-cell development and function; however, their role in adipocyte functionality has not yet been investigated. Here, we report for the first time that Forkhead box P4 (FoxP4) is expressed at high levels in subcutaneous fat depots and mature thermogenic adipocytes. Through molecular and gene expression analyses, we revealed that FoxP4 is induced in response to thermogenic stimuli, both in vivo and in isolated cells, and is regulated directly by the heat shock factor protein 1 through a heat shock response element identified in the proximal promoter region of FoxP4. Further detailed analysis involving chromatin immunoprecipitation and luciferase assays demonstrated that FoxP4 directly controls the levels of uncoupling protein 1, a key regulator of thermogenesis that uncouples fatty acid oxidation from ATP production. In addition, through our gain-of-function and loss-of-function studies, we showed that FoxP4 regulates the expression of a number of classic brown and beige fat genes and affects oxygen consumption in isolated adipocytes. Overall, our data demonstrate for the first time the novel role of FoxP4 in the regulation of thermogenic adipocyte functionality.
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spelling pubmed-84112332021-09-02 The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes Perie, Luce Verma, Narendra Mueller, Elisabetta J Lipid Res Research Article Forkhead box transcription factors have been shown to be involved in various developmental and differentiation processes. In particular, members of the FoxP family have been previously characterized in depth for their participation in the regulation of lung and neuronal cell differentiation and T-cell development and function; however, their role in adipocyte functionality has not yet been investigated. Here, we report for the first time that Forkhead box P4 (FoxP4) is expressed at high levels in subcutaneous fat depots and mature thermogenic adipocytes. Through molecular and gene expression analyses, we revealed that FoxP4 is induced in response to thermogenic stimuli, both in vivo and in isolated cells, and is regulated directly by the heat shock factor protein 1 through a heat shock response element identified in the proximal promoter region of FoxP4. Further detailed analysis involving chromatin immunoprecipitation and luciferase assays demonstrated that FoxP4 directly controls the levels of uncoupling protein 1, a key regulator of thermogenesis that uncouples fatty acid oxidation from ATP production. In addition, through our gain-of-function and loss-of-function studies, we showed that FoxP4 regulates the expression of a number of classic brown and beige fat genes and affects oxygen consumption in isolated adipocytes. Overall, our data demonstrate for the first time the novel role of FoxP4 in the regulation of thermogenic adipocyte functionality. American Society for Biochemistry and Molecular Biology 2021-08-09 /pmc/articles/PMC8411233/ /pubmed/34384787 http://dx.doi.org/10.1016/j.jlr.2021.100102 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Perie, Luce
Verma, Narendra
Mueller, Elisabetta
The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes
title The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes
title_full The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes
title_fullStr The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes
title_full_unstemmed The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes
title_short The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes
title_sort forkhead box transcription factor foxp4 regulates thermogenic programs in adipocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411233/
https://www.ncbi.nlm.nih.gov/pubmed/34384787
http://dx.doi.org/10.1016/j.jlr.2021.100102
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