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The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice

OBJECTIVE: Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue (BAT), a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPARα) in cold-induced brown...

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Autores principales: Defour, Merel, Dijk, Wieneke, Ruppert, Philip, Nascimento, Emmani B.M., Schrauwen, Patrick, Kersten, Sander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985232/
https://www.ncbi.nlm.nih.gov/pubmed/29455954
http://dx.doi.org/10.1016/j.molmet.2018.01.023
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author Defour, Merel
Dijk, Wieneke
Ruppert, Philip
Nascimento, Emmani B.M.
Schrauwen, Patrick
Kersten, Sander
author_facet Defour, Merel
Dijk, Wieneke
Ruppert, Philip
Nascimento, Emmani B.M.
Schrauwen, Patrick
Kersten, Sander
author_sort Defour, Merel
collection PubMed
description OBJECTIVE: Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue (BAT), a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPARα) in cold-induced browning. Here we aimed to investigate the importance of PPARα in driving transcriptional changes during cold-induced browning in mice. METHODS: Male wildtype and PPARα−/− mice were housed at thermoneutrality (28 °C) or cold (5 °C) for 10 days. Whole genome expression analysis was performed on inguinal WAT. In addition, other analyses were carried out. Whole genome expression data of livers of wildtype and PPARα−/− mice fasted for 24 h served as positive control for PPARα-dependent gene regulation. RESULTS: Cold exposure increased food intake and decreased weight of BAT and WAT to a similar extent in wildtype and PPARα−/− mice. Except for plasma non-esterified fatty acids, none of the cold-induced changes in plasma metabolites were dependent on PPARα genotype. Histological analysis of inguinal WAT showed clear browning upon cold exposure but did not reveal any morphological differences between wildtype and PPARα−/− mice. Transcriptomics analysis of inguinal WAT showed a marked effect of cold on overall gene expression, as revealed by principle component analysis and hierarchical clustering. However, wildtype and PPARα−/− mice clustered together, even after cold exposure, indicating a similar overall gene expression profile in the two genotypes. Pathway analysis revealed that cold upregulated pathways involved in energy usage, oxidative phosphorylation, and fatty acid β-oxidation to a similar extent in wildtype and PPARα−/− mice. Furthermore, cold-mediated induction of genes related to thermogenesis such as Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was similar in wildtype and PPARα−/− mice. Finally, pharmacological PPARα activation had a minimal effect on expression of cold-induced genes in murine WAT. CONCLUSION: Cold-induced changes in gene expression in inguinal WAT are unaltered in mice lacking PPARα, indicating that PPARα is dispensable for cold-induced browning.
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spelling pubmed-59852322018-06-05 The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice Defour, Merel Dijk, Wieneke Ruppert, Philip Nascimento, Emmani B.M. Schrauwen, Patrick Kersten, Sander Mol Metab Original Article OBJECTIVE: Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue (BAT), a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPARα) in cold-induced browning. Here we aimed to investigate the importance of PPARα in driving transcriptional changes during cold-induced browning in mice. METHODS: Male wildtype and PPARα−/− mice were housed at thermoneutrality (28 °C) or cold (5 °C) for 10 days. Whole genome expression analysis was performed on inguinal WAT. In addition, other analyses were carried out. Whole genome expression data of livers of wildtype and PPARα−/− mice fasted for 24 h served as positive control for PPARα-dependent gene regulation. RESULTS: Cold exposure increased food intake and decreased weight of BAT and WAT to a similar extent in wildtype and PPARα−/− mice. Except for plasma non-esterified fatty acids, none of the cold-induced changes in plasma metabolites were dependent on PPARα genotype. Histological analysis of inguinal WAT showed clear browning upon cold exposure but did not reveal any morphological differences between wildtype and PPARα−/− mice. Transcriptomics analysis of inguinal WAT showed a marked effect of cold on overall gene expression, as revealed by principle component analysis and hierarchical clustering. However, wildtype and PPARα−/− mice clustered together, even after cold exposure, indicating a similar overall gene expression profile in the two genotypes. Pathway analysis revealed that cold upregulated pathways involved in energy usage, oxidative phosphorylation, and fatty acid β-oxidation to a similar extent in wildtype and PPARα−/− mice. Furthermore, cold-mediated induction of genes related to thermogenesis such as Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was similar in wildtype and PPARα−/− mice. Finally, pharmacological PPARα activation had a minimal effect on expression of cold-induced genes in murine WAT. CONCLUSION: Cold-induced changes in gene expression in inguinal WAT are unaltered in mice lacking PPARα, indicating that PPARα is dispensable for cold-induced browning. Elsevier 2018-02-09 /pmc/articles/PMC5985232/ /pubmed/29455954 http://dx.doi.org/10.1016/j.molmet.2018.01.023 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Defour, Merel
Dijk, Wieneke
Ruppert, Philip
Nascimento, Emmani B.M.
Schrauwen, Patrick
Kersten, Sander
The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice
title The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice
title_full The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice
title_fullStr The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice
title_full_unstemmed The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice
title_short The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice
title_sort peroxisome proliferator-activated receptor α is dispensable for cold-induced adipose tissue browning in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985232/
https://www.ncbi.nlm.nih.gov/pubmed/29455954
http://dx.doi.org/10.1016/j.molmet.2018.01.023
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