Sox17 regulates liver lipid metabolism and adaptation to fasting

Samuel Rommelaere, Virginie Millet, Thien Phong Vu Manh, Thomas Gensollen, Pierre Andreoletti, Mustapha Cherkaoui-Malki, Christophe Bourges, Bertrand Escalière, Xin Du, Yu Xia, Jean Imbert, Bruce Beutler, Yoshiakira Kanai, Bernard Malissen, Marie Malissen, Anne Tailleux, Bart Staels, Franck Galland, Philippe Naquet

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e104925
JournalPLoS One
Volume9
Issue number8
DOIs
StatePublished - 2014

Fingerprint

PPAR alpha
Lipid Metabolism
lipid metabolism
Liver
fasting
Fasting
liver
mice
Chemical activation
Serum
transcriptomics
Phenotype
phenotype
mutants
Genes
Fenofibrate
Peroxisome Proliferator-Activated Receptors
beta oxidation
Biomarkers
Modulators

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rommelaere, S., Millet, V., Vu Manh, T. P., Gensollen, T., Andreoletti, P., Cherkaoui-Malki, M., ... Naquet, P. (2014). Sox17 regulates liver lipid metabolism and adaptation to fasting. PLoS One, 9(8), e104925. https://doi.org/10.1371/journal.pone.0104925

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.

In: PLoS One, Vol. 9, No. 8, 2014, p. e104925.

Research output: Contribution to journalArticle

Rommelaere, S, Millet, V, Vu Manh, TP, Gensollen, T, Andreoletti, P, Cherkaoui-Malki, M, Bourges, C, Escalière, B, Du, X, Xia, Y, Imbert, J, Beutler, B, Kanai, Y, Malissen, B, Malissen, M, Tailleux, A, Staels, B, Galland, F & Naquet, P 2014, 'Sox17 regulates liver lipid metabolism and adaptation to fasting', PLoS One, vol. 9, no. 8, pp. e104925. https://doi.org/10.1371/journal.pone.0104925
Rommelaere S, Millet V, Vu Manh TP, Gensollen T, Andreoletti P, Cherkaoui-Malki M et al. Sox17 regulates liver lipid metabolism and adaptation to fasting. PLoS One. 2014;9(8):e104925. https://doi.org/10.1371/journal.pone.0104925
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. In: PLoS One. 2014 ; Vol. 9, No. 8. pp. e104925.
@article{27d4cf912ff24accbf7723d393df1f7b,
title = "Sox17 regulates liver lipid metabolism and adaptation to fasting",
abstract = "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.",
author = "Samuel Rommelaere and Virginie Millet and {Vu Manh}, {Thien Phong} and Thomas Gensollen and Pierre Andreoletti and Mustapha Cherkaoui-Malki and Christophe Bourges and Bertrand Escali{\`e}re and Xin Du and Yu Xia and Jean Imbert and Bruce Beutler and Yoshiakira Kanai and Bernard Malissen and Marie Malissen and Anne Tailleux and Bart Staels and Franck Galland and Philippe Naquet",
year = "2014",
doi = "10.1371/journal.pone.0104925",
language = "English (US)",
volume = "9",
pages = "e104925",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - Sox17 regulates liver lipid metabolism and adaptation to fasting

AU - Rommelaere, Samuel

AU - Millet, Virginie

AU - Vu Manh, Thien Phong

AU - Gensollen, Thomas

AU - Andreoletti, Pierre

AU - Cherkaoui-Malki, Mustapha

AU - Bourges, Christophe

AU - Escalière, Bertrand

AU - Du, Xin

AU - Xia, Yu

AU - Imbert, Jean

AU - Beutler, Bruce

AU - Kanai, Yoshiakira

AU - Malissen, Bernard

AU - Malissen, Marie

AU - Tailleux, Anne

AU - Staels, Bart

AU - Galland, Franck

AU - Naquet, Philippe

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84929051811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929051811&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0104925

DO - 10.1371/journal.pone.0104925

M3 - Article

VL - 9

SP - e104925

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 8

ER -