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Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting

Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up...

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Autores principales: Rommelaere, Samuel, Millet, Virginie, Vu Manh, Thien-Phong, Gensollen, Thomas, Andreoletti, Pierre, Cherkaoui-Malki, Mustapha, Bourges, Christophe, Escalière, Bertrand, Du, Xin, Xia, Yu, Imbert, Jean, Beutler, Bruce, Kanai, Yoshiakira, Malissen, Bernard, Malissen, Marie, Tailleux, Anne, Staels, Bart, Galland, Franck, Naquet, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139292/
https://www.ncbi.nlm.nih.gov/pubmed/25141153
http://dx.doi.org/10.1371/journal.pone.0104925
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author Rommelaere, Samuel
Millet, Virginie
Vu Manh, Thien-Phong
Gensollen, Thomas
Andreoletti, Pierre
Cherkaoui-Malki, Mustapha
Bourges, Christophe
Escalière, Bertrand
Du, Xin
Xia, Yu
Imbert, Jean
Beutler, Bruce
Kanai, Yoshiakira
Malissen, Bernard
Malissen, Marie
Tailleux, Anne
Staels, Bart
Galland, Franck
Naquet, Philippe
author_facet Rommelaere, Samuel
Millet, Virginie
Vu Manh, Thien-Phong
Gensollen, Thomas
Andreoletti, Pierre
Cherkaoui-Malki, Mustapha
Bourges, Christophe
Escalière, Bertrand
Du, Xin
Xia, Yu
Imbert, Jean
Beutler, Bruce
Kanai, Yoshiakira
Malissen, Bernard
Malissen, Marie
Tailleux, Anne
Staels, Bart
Galland, Franck
Naquet, Philippe
author_sort Rommelaere, Samuel
collection PubMed
description Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/− mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.
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spelling pubmed-41392922014-08-25 Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting Rommelaere, Samuel Millet, Virginie Vu Manh, Thien-Phong Gensollen, Thomas Andreoletti, Pierre Cherkaoui-Malki, Mustapha Bourges, Christophe Escalière, Bertrand Du, Xin Xia, Yu Imbert, Jean Beutler, Bruce Kanai, Yoshiakira Malissen, Bernard Malissen, Marie Tailleux, Anne Staels, Bart Galland, Franck Naquet, Philippe PLoS One Research Article Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/− mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting. Public Library of Science 2014-08-20 /pmc/articles/PMC4139292/ /pubmed/25141153 http://dx.doi.org/10.1371/journal.pone.0104925 Text en © 2014 Rommelaere et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rommelaere, Samuel
Millet, Virginie
Vu Manh, Thien-Phong
Gensollen, Thomas
Andreoletti, Pierre
Cherkaoui-Malki, Mustapha
Bourges, Christophe
Escalière, Bertrand
Du, Xin
Xia, Yu
Imbert, Jean
Beutler, Bruce
Kanai, Yoshiakira
Malissen, Bernard
Malissen, Marie
Tailleux, Anne
Staels, Bart
Galland, Franck
Naquet, Philippe
Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting
title Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting
title_full Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting
title_fullStr Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting
title_full_unstemmed Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting
title_short Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting
title_sort sox17 regulates liver lipid metabolism and adaptation to fasting
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139292/
https://www.ncbi.nlm.nih.gov/pubmed/25141153
http://dx.doi.org/10.1371/journal.pone.0104925
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