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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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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. |
format | Online Article Text |
id | pubmed-8411233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
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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