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<title lang=en>A systems biology approach to the hepatic role of the oxysterol receptor LXR in the regulation of lipogenesis highlights a cross-talk with PPARα.</title>
<creator>Ducheix, Simon</creator>
<creator>Podechard, Normand</creator>
<creator>Lasserre, Frédéric</creator>
<creator>Polizzi, Arnaud</creator>
<creator>Pommier, Aurélien</creator>
<creator>Murzilli, Stefania</creator>
<creator>Di Lisio, Chiara</creator>
<creator>D'Amore, Simona</creator>
<creator>Bertrand-Michel, Justine</creator>
<creator>Montagner, Alexandra</creator>
<creator>Pineau, Thierry</creator>
<creator>Loiseau, Nicolas</creator>
<creator>Lobaccaro, Jean-Marc A.</creator>
<creator>Martin, Pascal, </creator>
<creator>Guillou, Hervé</creator>
<contributor>ToxAlim (ToxAlim) ; Institut National Polytechnique [Toulouse] (INP) - Institut National de la Recherche Agronomique (INRA) - Université Paul Sabatier - Toulouse 3 (UPS) - Ecole Nationale Vétérinaire de Toulouse</contributor>
<contributor>Stress, membrane, signalisation ; ToxAlim (ToxAlim) ; Institut National Polytechnique [Toulouse] (INP) - Institut National de la Recherche Agronomique (INRA) - Université Paul Sabatier - Toulouse 3 (UPS) - Ecole Nationale Vétérinaire de Toulouse - Institut National Polytechnique [Toulouse] (INP) - Institut National de la Recherche Agronomique (INRA) - Université Paul Sabatier - Toulouse 3 (UPS) - Ecole Nationale Vétérinaire de Toulouse - Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) - Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Génétique, reproduction et développement (GReD) ; Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR79 - Université d'Auvergne - Clermont-Ferrand I (UdA) - Université Blaise Pascal - Clermont-Ferrand 2 (UBP)</contributor>
<contributor>Unité de Nutrition Humaine (UNH) ; Institut National de la Recherche Agronomique (INRA) - Université d'Auvergne - Clermont-Ferrand I (UdA) - Clermont Université</contributor>
<contributor>Laboratory of Lipid Metabolism and Cancer ; Consorzio Mario NegriSud</contributor>
<contributor>Plateau MetaToul-LIPIDOMIQUE ; Institut National de la Santé et de la Recherche Médicale (INSERM) - MetaToul, Plateau de lipidomique</contributor>
<contributor>Centre de Physiopathologie Toulouse Purpan ; Université Paul Sabatier - Toulouse 3 (UPS) - IFR30 - IFR150 - Institut National de la Santé et de la Recherche Médicale (INSERM)</contributor>
<description>International audience</description>
<source>ISSN: 0300-9084</source>
<source>Biochimie</source>
<publisher>Elsevier</publisher>
<identifier>inserm-00872582</identifier>
<identifier>http://www.hal.inserm.fr/inserm-00872582</identifier>
<source>http://www.hal.inserm.fr/inserm-00872582</source>
<source>Biochimie, Elsevier, 2013, 95 (3), pp.556-67. 〈10.1016/j.biochi.2012.09.028〉</source>
<identifier>DOI : 10.1016/j.biochi.2012.09.028</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biochi.2012.09.028</relation>
<identifier>PUBMED : 23063693</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/23063693</relation>
<language>en</language>
<subject lang=es>Oxysterol</subject>
<subject lang=es>LXR</subject>
<subject lang=es>PPARα</subject>
<subject lang=es>Lipogenesis</subject>
<subject lang=es>Steatosis</subject>
<subject>[SDV.GEN] Life Sciences [q-bio]/Genetics</subject>
<subject>[SDV.BC] Life Sciences [q-bio]/Cellular Biology</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>The Liver X Receptors (LXRs) α and β and the Peroxisome Proliferator-Activated Receptor α (PPARα) are transcription factors that belong to class II nuclear receptors. They drive the expression of genes involved in hepatic lipid homeostasis and therefore are important targets for the prevention and treatment of nonalcoholic fatty liver disease (NAFLD). LXRs and PPARα are regulated by endogenous ligands, oxysterols and fatty acid derived molecules, respectively. In the liver, pharmacological activation of LXRs leads to the over-expression of genes involved in de novo lipogenesis, while PPARα is critical for fatty acid catabolism in nutrient deprivation. Even if these two nuclear receptors seemed to play opposite parts, recent studies have highlighted that PPARα also influence the expression of genes involved in fatty acids synthesis. In this study, we used pharmacological approaches and genetically engineered mice to investigate the cross-talk between LXRs and PPARα in the regulation of genes responsible for lipogenesis. We first investigated the effect of T0901317 and fenofibrate, two synthetic agonists of LXRs and PPARα, respectively. As expected, T0901317 and fenofibrate induce expression of genes involved LXR-dependent and PPARα-dependent lipogenic responses. Considering such overlapping effect, we then tested whether LXR agonist may influence PPARα driven response and vice versa. We show that the lack of PPARα does not influence the effects of T0901317 on lipogenic genes expression. However, PPARα deficiency prevents the up-regulation of genes involved in ω-hydroxylation that are induced by the LXR agonist. In addition, over-expression of lipogenic genes in response to fenofibrate is decreased in LXR knockout mice as well as the expression of PPARα target genes involved in fatty acid oxidation. Altogether, our work provides in vivo evidence for a central interconnection between nuclear receptors that drive hepatic lipid metabolism in response to oxysterol and fatty acids.</description>
<date>2013-03</date>
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