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183 results on '"Justine BERTRAND-MICHEL"'

101. Liquid Chromatography-High Resolution Mass Spectrometry Method to Study Sphingolipid Metabolism Changes in Response to CD95L

Author: Fatima, Bilal, Michaël, Pérès, Pauline, Le Faouder, Aude, Dupuy, Justine, Bertrand-Michel, Nathalie, Andrieu-Abadie, Thierry, Levade, Bassam, Badran, Ahmad, Daher, and Bruno, Ségui
Subjects: Sphingolipids, Fas Ligand Protein, Apoptosis, Ceramides, Lipid Metabolism, Mass Spectrometry, Chromatography, Liquid, Protein Binding
Abstract: Sphingolipids are sphingoid base-containing lipids, among which some metabolites behave as bioactive molecules in various biological processes, including cell death. Whereas ceramide is now viewed as an anti-oncometabolite, leading to cancer cell death, CD95L-induced apoptosis is associated with sphingolipid changes, which likely contribute to caspase-dependent signaling pathway activation. Here, we describe Liquid Chromatography-high resolution mass spectrometry method (LC-HRMS) to analyze sphingolipid metabolism changes triggered by CD95L.
Published: 2017

102. Characterization of the lipid envelope of exosome encapsulated HEV particles protected from the immune response

Author: Jacques Izopet, Martine Dubois, Pierre-Emmanuel Gleizes, Tiffany Bonnefois, Florence Abravanel, Célia Plisson-Chastang, Sabine Chapuy-Regaud, Justine Bertrand-Michel, Benoit Flan, Steve Simoneau, Sébastien Lhomme, Bruno You, Laboratoire de Virologie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Laboratoire de biologie moléculaire eucaryote (LBME), Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie Intégrative (CBI), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Ecole des Ingénieurs de la Ville de Paris, MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche et de Diagnostic sur le Sida [Abidjan, Côte d'Ivoire] (CeDreS), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), LFB Biomédicaments, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Contrôle des maladies animales exotiques et émergentes (UMR CMAEE), Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Plateforme Metatoul, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche et de Diagnostic sur le Sida (CeDreS), CHU Treichville, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: 0301 basic medicine, viruses, [SDV]Life Sciences [q-bio], 030106 microbiology, Population, medicine.disease_cause, Exosomes, Biochemistry, Exosome, Microbiology, 03 medical and health sciences, Membrane Lipids, Hepatitis E virus, Viral envelope, Cell-Derived Microparticles, medicine, Humans, education, ComputingMilieux_MISCELLANEOUS, Infectivity, education.field_of_study, biology, virus diseases, RNA virus, General Medicine, Hep G2 Cells, biology.organism_classification, Virology, digestive system diseases, Microvesicles, 3. Good health, Hepatitis E, 030104 developmental biology, biology.protein, Antibody
Abstract: The hepatitis E virus (HEV) is the most common cause of acute hepatitis worldwide. Although HEV is a small, naked RNA virus, HEV particles become associated with lipids in the blood of infected patients and in the supernatant of culture systems. The egress of these particles from cells implies the exocytosis pathway but the question of the role of the resulting HEV RNA containing exosomes and the nature of the lipids they contain has not been fully addressed. We determined the lipid proportions of exosomes from uninfected and HEV-infected cells and their role in HEV spreading. We cultured a suitable HEV strain on HepG2/C3A cells and analyzed the population of exosomes containing HEV RNA using lipidomics methods and electron microscopy. We also quantified HEV infectivity using an infectivity endpoint method based on HEV RNA quantification to calculate the tissue culture infectious dose 50. Exosomes produced by HEV-infected HepG2/C3A cells contained encapsidated HEV RNA. These HEV RNA-containing exosomes were infectious but ten times less than stools. HEV from stools, but not exosome-associated HEV from culture supernatant, was neutralized by anti-HEV antibodies in a dose-dependent manner. HEV infection did not influence the morphology or lipid proportions of the bulk of exosomes. These exosomes contained significantly more cholesterol, phosphatidylserine, sphingomyelin and ceramides than the parent cells, but less phosphoinositides and polyunsaturated fatty acids. Exosomes play a major role in HEV egress but HEV infection does not modify the characteristics of the bulk of exosomes produced by infected cells. PS and cholesterol enriched in these vesicles could then be critical for HEV entry. HEV particles in exosomes are protected from the immune response which could lead to the wide circulation of HEV in its host.
Published: 2017
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103. Identification of signaling pathways targeted by the food contaminant FB1: Transcriptome and kinome analysis of samples from pig liver and intestine

Author: Anne-Marie Cossalter, Justine Bertrand-Michel, Joëlle Laffite, Jean-Denis Bailly, Isabelle P. Oswald, Hervé Guillou, Pascal Gourbeyre, Ana Paula Frederico Rodrigues Loureiro Bracarense, Nicolas Loiseau, Scott Napper, Marion Régnier, Yannick Lippi, Philippe Pinton, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), International Vaccine Center, University of Saskatchewan [Saskatoon] (U of S), Department of Biochemistry, Hôpital Lapeyronie, MetaToul-Lipidomic Facility-MetaboHUB, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Laboratory of Animal Pathology, Universidade Estadual de Londrina, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Plateforme Ezop (Ezop), Transcriptomic impact of Xenobiotics (E23 TRiX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), State University of Londrina = Universidade Estadual de Londrina, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Loiseau, Nicolas, and Oswald, Isabelle P.
Subjects: Male, 0301 basic medicine, Integrins, [SDV]Life Sciences [q-bio], Food Contamination, Pharmacology, liver, Fumonisins, Transcriptome, 03 medical and health sciences, chemistry.chemical_compound, fumonisin, Animals, PTEN, Kinome, Protein Interaction Maps, Phosphorylation, jejunum, Acute-Phase Reaction, Protein kinase B, PI3K/AKT/mTOR pathway, Fumonisin B1, biology, Akt/PKB signaling pathway, Gene Expression Profiling, Fatty Acids, PI3K-AKT signaling, swine, Proteins, Protein phosphatase 2, Mycotoxins, Lipid Metabolism, Molecular biology, 3. Good health, Intestines, 030104 developmental biology, Gene Expression Regulation, chemistry, biology.protein, Signal Transduction, Food Science, Biotechnology
Abstract: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium species. In mammals, this toxin causes widespread organ-specific damage; it promotes hepatotoxicity, is immunotoxic, alters intestinal functions… Despite its inhibitory effect on de novo ceramide synthesis, its molecular mechanism of action and toxicity are not totally elucidated. To explore the mechanism of FB1 toxicity, we analyzed the transcriptome and kinome of two organs targeted by FB1: the liver and the jejunum. Pigs were fed for 4 weeks on a control diet or a FB1-contaminated diet (10 mg/kg). As expected, FB1-exposed pigs gained less weight and displayed a higher sphinganine/sphingosine ratio. Comparison of the transcriptomes and the kinomes of treated versus control pigs showed striking differences. Among the disrupted pathways in liver and jejunum, we highlight Protein Kinase B (AKT) / Phosphatase and tensin homolog (PTEN) at the intersection of the FB1-modulated pathways. Most of the effects of FB1 are mediated by the regulation of ceramide level, which influences protein phosphatase 2 (PP2A) and the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. This pathway might be a new target to counteract toxic effect of Fumonin B1 which are on of the most spread nutritional's contaminant in the world. This article is protected by copyright. All rights reserved.
Published: 2017
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104. Dietary oleic acid regulates hepatic lipogenesis through a liver X receptor-dependent signaling

Author: Alice Marmugi, Fadila Benhamed, Jean-Marc A. Lobaccaro, Marion Régnier, Hervé Guillou, Justine Bertrand-Michel, Alexandra Montagner, Simon Ducheix, Catherine Postic, Frédéric Lasserre, Pascal G.P. Martin, Nicolas Loiseau, Laurent Ferrier, Arnaud Polizzi, Laila Mselli-Lakhal, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MetaToul, Plateau de lipidomique, Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Université Blaise Pascal (Clermont Ferrand 2) (UBP), Clermont Université, Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Université Paris Descartes - Paris 5 (UPD5), Guillou, Hervé, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), MetaToul Lipidomics, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), ToxAlim ( ToxAlim ), Institut National Polytechnique [Toulouse] ( INP ) -Institut National de la Recherche Agronomique ( INRA ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse ( ENVT ), Institut National Polytechnique de Toulouse ( INPT ) -Institut National Polytechnique de Toulouse ( INPT ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), GReD, Centre National de la Recherche Scientifique ( CNRS ), Université Blaise Pascal (Clermont Ferrand 2) ( UBP ), Centre de Recherche en Nutrition Humaine d'Auvergne ( CRNH d'Auvergne ), and Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: Male, 0301 basic medicine, cholestérolemie, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, lcsh:Medicine, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Essential fatty acid, Plant Products, Medicine and Health Sciences, Protein Isoforms, lcsh:Science, Liver X Receptors, chemistry.chemical_classification, Multidisciplinary, Ecology, Liver Diseases, Fatty Acids, Fatty liver, Agriculture, Lipids, Trophic Interactions, 3. Good health, Cholesterol, Community Ecology, Liver, 030220 oncology & carcinogenesis, Models, Animal, Lipogenesis, Alimentation et Nutrition, lipids (amino acids, peptides, and proteins), Signal transduction, acide oléique, Research Article, medicine.medical_specialty, Transgene, Immunoblotting, Mice, Transgenic, Gastroenterology and Hepatology, Biology, cholesteremia, Vegetable Oils, 03 medical and health sciences, Internal medicine, medicine, Animals, Food and Nutrition, Liver X receptor, Olive Oil, Nutrition, Inflammation, Gene Expression Profiling, Ecology and Environmental Sciences, lcsh:R, Biology and Life Sciences, medicine.disease, Animal Feed, Dietary Fats, Agronomy, Diet, Fatty Liver, Mice, Inbred C57BL, Oleic acid, Metabolism, 030104 developmental biology, Endocrinology, chemistry, lcsh:Q, lipogénèse hépatique, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Oleic Acid, Crop Science
Abstract: Olive oil consumption is beneficial for health as it is associated with a decreased prevalence of cancer and cardiovascular diseases. Oleic acid is, by far, the most abundant component of olive oil. Since it can be made through de novo synthesis in animals, it is not an essential fatty acid. While it has become clear that dietary oleic acid regulates many biological processes, the signaling pathway involved in these regulations remains poorly defined. In this work we tested the impact of an oleic acid-rich diet on hepatic gene expression. We were particularly interested in addressing the contribution of Liver X Receptors (LXR) in the control of genes involved in hepatic lipogenesis, an essential process in whole body energy homeostasis. We used wild-type mice and transgenic mice deficient for both α and β Liver X Receptor isoforms (LXR-/-) fed a control or an oleate enriched diet. We observed that hepatic-lipid accumulation was enhanced as well as the expression of lipogenic genes in the liver of wild-type mice fed the oleate enriched diet. In contrast, none of these changes occurred in the liver of LXR-/- mice. Strikingly, oleate-rich diet reduced cholesterolemia in wild-type mice and induced signs of liver inflammation and damage in LXR-/- mice but not in wild-type mice. This work suggests that dietary oleic acid reduces cholesterolemia while promoting LXR-dependent hepatic lipogenesis without detrimental effects to the liver.
Published: 2017
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105. Acid Ceramidase Deficiency in Mice Results in a Broad Range of Central Nervous System Abnormalities

Author: Thierry Levade, David R. Hampson, Matthew C. Micsenyi, Tomo Sawada, Jakub Sikora, Josefina Casas, Pauline Le Faouder, Christopher K. Dunn, Aude Dupuy, Mustafa Kamani, Shaalee Dworski, E. Ellen Jones, Justine Bertrand-Michel, Richard R. Drake, Ingrid Cong Yang Xuan, Jeffrey A. Medin, Gemma Fabriàs, Steven U. Walkley, Ministerio de Economía y Competitividad (España), Fabriàs, Gemma [0000-0001-7162-3772], and Fabriàs, Gemma
Subjects: Central Nervous System, 0301 basic medicine, Pathology, medicine.medical_specialty, Time Factors, Acid Ceramidase, Central nervous system, Mice, Transgenic, Motor Activity, Biology, Nervous System Malformations, Pathology and Forensic Medicine, Ceramide, Mice, 03 medical and health sciences, 0302 clinical medicine, Cerebellum, Acid ceramide, medicine, Animals, Cerebrum, Neurons, Farber disease, Sphingolipids, Thigmotaxis, Behavior, Animal, Microglia, Homozygote, Neurodegeneration, Regular Article, medicine.disease, 3. Good health, Farber Lipogranulomatosis, Phenotype, 030104 developmental biology, medicine.anatomical_structure, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, ASAH1, Choroid plexus, 030217 neurology & neurosurgery, Hydrocephalus
Abstract: arber disease is a rare autosomal recessive disorder caused by acid ceramidase deficiency that usually presents as early-onset progressive visceral and neurologic disease. To understand the neurologic abnormality, we investigated behavioral, biochemical, and cellular abnormalities in the central nervous system of Asah1P361R/P361R mice, which serve as a model of Farber disease. Behaviorally, the mutant mice had reduced voluntary locomotion and exploration, increased thigmotaxis, abnormal spectra of basic behavioral activities, impaired muscle grip strength, and defects in motor coordination. A few mutant mice developed hydrocephalus. Mass spectrometry revealed elevations of ceramides, hydroxy-ceramides, dihydroceramides, sphingosine, dihexosylceramides, and monosialodihexosylganglioside in the brain. The highest accumulation was in hydroxy-ceramides. Storage compound distribution was analyzed by mass spectrometry imaging and morphologic analyses and revealed involvement of a wide range of central nervous system cell types (eg, neurons, endothelial cells, and choroid plexus cells), most notably microglia and/or macrophages. Coalescing and mostly perivascular granuloma–like accumulations of storage-laden CD68+ microglia and/or macrophages were seen as early as 3 weeks of age and located preferentially in white matter, periventricular zones, and meninges. Neurodegeneration was also evident in specific cerebral areas in late disease. Overall, our central nervous system studies in Asah1P361R/P361R mice substantially extend the understanding of human Farber disease and suggest that this model can be used to advance therapeutic approaches for this currently untreatable disorder. © 2017 American Society for Investigative Pathology, Supported by National Institute of Neurological Diseases and Stroke Award 1F05 NS074790, Charles University Research Development Schemes (PRVOUK) grant P24/LF1/3, and OPPK grant CZ.2.16/3.1.00/24509 (J.S.); the Canadian Institutes of Health Research Biological Therapeutics Traineeship (S.D.); NIH grants 1R21NS078191-01A1 (J.A.M.), R01 HD045561 (S.U.W.), and P30 HD071593 (S.U.W.); Spanish Ministries of Science and Technology grant SAF2011-22444 and Economy and Competitiveness grant CTQ2014-54743-R (J.C. and G.F.); INSERM (T.L.); Vaincre les Maladies Lysosomales (T.L. and J.A.M.); and the South Carolina SmartState Endowed Research program, National Cancer Institute grant P30 CA138313 and South Carolina Clinical and Translational Research Institute grants UL1 RR029882 and UL1 TR000062 (R.R.D.).
Published: 2017

106. Liquid Chromatography–High Resolution Mass Spectrometry Method to Study Sphingolipid Metabolism Changes in Response to CD95L

Author: Thierry Levade, Bruno Ségui, Bassam Badran, Justine Bertrand-Michel, Nathalie Andrieu-Abadie, Pauline Le Faouder, Fatima Bilal, Aude Dupuy, Michaël Pérès, and Ahmad Daher
Subjects: 0301 basic medicine, Programmed cell death, Ceramide, Chromatography, Chemistry, Lipid metabolism, Sphingolipid, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Apoptosis, Cancer cell, lipids (amino acids, peptides, and proteins), Signal transduction, Sphingomyelin
Abstract: Sphingolipids are sphingoid base-containing lipids, among which some metabolites behave as bioactive molecules in various biological processes, including cell death. Whereas ceramide is now viewed as an anti-oncometabolite, leading to cancer cell death, CD95L-induced apoptosis is associated with sphingolipid changes, which likely contribute to caspase-dependent signaling pathway activation. Here, we describe Liquid Chromatography-high resolution mass spectrometry method (LC-HRMS) to analyze sphingolipid metabolism changes triggered by CD95L.
Published: 2017
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107. Characterization of a Bvg-regulated fatty acid methyl-transferase in Bordetella pertussis

Author: Loïc Coutte, David Hot, Elodie Lesne, Véronique Dhennin, Alex Rivera-Millot, Philippe Froguel, Camille Locht, Françoise Jacob-Dubuisson, Rudy Antoine, Luis Solans, and Justine Bertrand-Michel
Subjects: 0301 basic medicine, Bordetella pertussis, Bordetella, Molecular biology, Physiology, Whooping Cough, Complement System, lcsh:Medicine, Plant Science, Fatty Acids, Nonesterified, Pathology and Laboratory Medicine, Biochemistry, Sequencing techniques, Immune Physiology, Medicine and Health Sciences, Virulence Factors, Bordetella, lcsh:Science, Pathogen, chemistry.chemical_classification, Immune System Proteins, Multidisciplinary, biology, Plant Bacterial Pathogens, Fatty Acids, RNA sequencing, Lipids, Recombinant Proteins, Bacterial Pathogens, Medical Microbiology, Host-Pathogen Interactions, Pathogens, Research Article, Signal Transduction, Immunology, Plant Pathogens, Virulence, Microbiology, Regulon, Gene product, 03 medical and health sciences, Extraction techniques, Bacterial Proteins, Humans, Microbial Pathogens, Gene, Bacteria, lcsh:R, Organisms, Biology and Life Sciences, Proteins, Fatty acid, Gene Expression Regulation, Bacterial, Methyltransferases, Plant Pathology, biology.organism_classification, RNA extraction, Research and analysis methods, Molecular biology techniques, 030104 developmental biology, chemistry, Immune System, lcsh:Q
Abstract: The whooping cough agent Bordetella pertussis controls the expression of its large virulence regulon in a coordinated manner through the two-component signal transduction system BvgAS. In addition to the genes coding for bona fide virulence factors, the Bvg regulon comprises genes of unknown function. In this work, we characterized a new Bvg-activated gene called BP2936. Homologs of BP2936 are found in other pathogenic Bordetellae and in several other species, including plant pathogens and environmental bacteria. We showed that the gene product of BP2936 is a membrane-associated methyl-transferase of free fatty acids. We thus propose to name it FmtB, for fatty acid methyl-transferase of Bordetella. The role of this protein was tested in cellular and animal models of infection, but the loss of BP2936 did not appear to affect host-pathogen interactions in those assays. The high level of conservation of BP2936 among B. pertussis isolates nevertheless argues that it probably plays a role in the life cycle of this pathogen.
Published: 2017

108. Vitamin D supplementation restores the blunted muscle protein synthesis response in deficient old rats through an impact on ectopic fat deposition

Author: Yvette C. Luiking, Jérôme Salles, Camille Tagliaferri, Alexandre Berry, Yves Boirie, Carla Domingues-Faria, Justine Bertrand-Michel, Philippe Denis, Sjors Verlaan, Miriam van Dijk, Corinne Pouyet, Christelle Guillet, Stéphane Walrand, Christophe Giraudet, Audrey Chanet, Katia Bouton, Marion Jourdan, Véronique Patrac, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Institut Claude de Préval (ICP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Nutricia Advanced Medical Nutrition, Danone Research, Nutrition Clinique, CHU Clermont-Ferrand, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Universitaire de Purpan (CHU Purpan), and Centre Hospitalier Universitaire de Clermont-Ferrand
Subjects: Male, 0301 basic medicine, Aging, Sarcopenia, carence en vitamine D, Anabolism, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Gene Expression, Muscle Proteins, Biochemistry, rat agé, anabolisme, Eating, chemistry.chemical_compound, 0302 clinical medicine, Vitamin D, Adiposity, 2. Zero hunger, Nutrition and Dietetics, Chemistry, anabolism, Organ Size, modèle expérimental, Body Composition, medicine.symptom, Signal Transduction, Vitamin, medicine.medical_specialty, 030209 endocrinology & metabolism, vitamin D deficiency, 03 medical and health sciences, Internal medicine, medicine, Vitamin D and neurology, Animals, Rats, Wistar, Intramyocellular lipids, Muscle, Skeletal, Molecular Biology, synthèse de protéine, Body Weight, protéine musculaire, Lipid Metabolism, Vitamin D Deficiency, medicine.disease, Muscle protein anabolism, 030104 developmental biology, Endocrinology, Dietary Supplements, Lean body mass, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, eIF2alpha signaling, Weight gain, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: The authors gratefully acknowledge all members of the animal facilities from Theix's INRA center for their valuable assistance in conducting this study; We investigated the impact of vitamin D deficiency and repletion on muscle anabolism in old rats. Animals were fed a control (1 IU vitamin D3/g, ctrl, n=20) or a vitamin D-depleted diet (VDD; 0 IU, n=30) for 6 months. A subset was thereafter sacrificed in the control (ctrl6) and depleted groups (VDD6). Remaining control animals were kept for 3 additional months on the same diet (ctrl9), while a part of VDD rats continued on a depleted diet (VDD9) and another part was supplemented with vitamin D (5 IU, VDS9). The ctr16 and VDD6 rats and the ctr19, VDD9 and VDS9 rats were 21 and 24 months old, respectively. Vitamin D status, body weight and composition, muscle strength, weight and lipid content were evaluated. Muscle protein synthesis rate (fractional synthesis rate; FSR) and the activation of controlling pathways were measured. VDD reduced plasma 25(OH)-vitamin D, reaching deficiency (
Published: 2017
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109. A genome scan for milk production traits in dairy goats reveals two new mutations in Dgat1 reducing milk fat content

Author: Gwenola Tosser-Klopp, Ines Racke, Philippe Bardou, Justine Bertrand-Michel, Isabelle Palhiere, Florent Woloszyn, Rachel Rupp, Hüseyin Besir, Julien Sarry, P. Martin, Kamila Canale-Tabet, Cyrielle Maroteau, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Division of Molecular and Clinical Medecine, University of Dundee, SIGENAE, MetaToul-Lipidomic Core Facility, MetaboHUB, Institut National de la Santé et de la Recherche Médicale (INSERM), Protein Expression and Purification Core Facility, European Molecular Biology Laboratory, PhénoFinLait, Région Midi-Pyrénées, École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ProdInra, Archive Ouverte, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: 0301 basic medicine, microsatellite, Animal breeding, milk, production, genome, dairy goat, mutation, Science, [SDV]Life Sciences [q-bio], Genome-wide association study, Biology, somatic cell score, coa diacylglycerol, medicine.disease_cause, Article, 03 medical and health sciences, Genetic variation, acyltransferase, medicine, genetic polymorphism, Gene, acid composition, 2. Zero hunger, Genetics, marker, Mutation, Multidisciplinary, 0402 animal and dairy science, 04 agricultural and veterinary sciences, 040201 dairy & animal science, Breed, [SDV] Life Sciences [q-bio], 030104 developmental biology, protein percentage, Medicine, Microsatellite, false discovery rate, linkage disequilibrium, Reference genome
Abstract: Un corrigendum de cet article a été publié dans le vol.8, Article 4060 avec la clé UT (WOS) 000426355200007 et le DOI : 10.1038/s41598-018-22118-x; The quantity of milk and milk fat and proteins are particularly important traits in dairy livestock.However, little is known about the regions of the genome that influence these traits in goats. Weconducted a genome wide association study in French goats and identified 109 regions associatedwith dairy traits. For a major region on chromosome 14 closely associated with fat content, theDiacylglycerol O-Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional candidategene. The caprine reference sequence of this gene was completed and 29 polymorphisms were found inthe gene sequence, including two novel exonic mutations: R251L and R396W, leading to substitutionsin the protein sequence. The R251L mutation was found in the Saanen breed at a frequency of 3.5% andthe R396W mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7% respectively.The R396W mutation explained 46% of the genetic variance of the trait, and the R251L mutation 6%.Both mutations were associated with a notable decrease in milk fat content. Their causality was thendemonstrated by a functional test. These results provide new knowledge on the genetic basis of milksynthesis and will help improve the management of the French dairy goat breeding program.
Published: 2017
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110. Insight into the contribution of isoprostanoids to the health effects of omega 3 PUFAs

Author: Thierry Durand, Jean-Marie Galano, Laurie Joumard-Cubizolles, Ho Hang Leung, Justine Bertrand-Michel, Claire Vigor, André Mazur, Jetty Chung-Yung Lee, Cécile Gladine, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), School of Biological Sciences, Faculty of Sciences, University of Hong Kong, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Ecole Nationale Supérieure de Chimie de Montpellier, UMR 1048, Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme MetaToul-Lipodomique, MetaToul, MetaboHUB, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul-MetaboHUB, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), MetaToul Lipidomics, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and MetaboHUB-MetaToul
Subjects: 0301 basic medicine, cardiovascular risk, Physiology, Isoprostanes, Isoprostanoids, Biochemistry, Omega, Omega 3 PUFAs, OMEGA-3 POLYUNSATURATED FATTY ACIDS, 03 medical and health sciences, Bioactive lipid mediators, 0302 clinical medicine, Lipidomics, Fatty Acids, Omega-3, Animals, Humans, Neuroprostanes, maladie inflammatoire, Pharmacology, chemistry.chemical_classification, Chemistry, Cell Biology, 3. Good health, inflammatory disease, 030104 developmental biology, risque cardiovasculaire, Docosahexaenoic acid, Biological significance, Health, acide gras polyinsaturé n-3, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Polyunsaturated fatty acid, rôle protecteur
Abstract: The authors received support for their previous and current studies on omega 3 IsoPs from INRA and the Groupe Lipides Nutrition; Omega 3 polyunsaturated fatty acids have been reported to confer beneficial health effects notably in the field of cardiovascular and inflammatory diseases. The current knowledge suggests a significant portion of the effects of omega 3 polyunsaturated fatty acids are mediated by their oxygenated metabolites. This review attempts to cover the current literature about the contribution of specific omega 3 oxygenated metabolites, namely omega 3 isoprostanoids, which are produced through free-radical mediated oxidation. A special emphasis has been given to the most biologically relevant omega 3 polyunsaturated fatty acids namely the alpha-linolenic, eicosapentaenoic and docosahexaenoic acids. The review includes a comprehensive description of the biosynthetic pathways, a summary of studies related to the biological significance of omega 3 isoprostanoids as well as a critical description of analytical development in the field of omega 3 isoprostanoids profiling in biological samples
Published: 2017
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111. Atypical cleavage of protonated N‐fatty acyl amino acids derived from aspartic acid evidenced by sequential MS3 experiments

Author: Anna Warnet, Pauline Le Faouder, Justine Bertrand-Michel, Mohammed Belbachir, Toufik Taalibi Boukerche, Sandra Alves, Jean-Claude Tabet, Mohamed Bouchekara, Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université d'Oran 1 Ahmed Ben Bella [Oran], Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University Mustapha Stambouli [Mascara], University Hassiba Benbouali, Chlef, Algeria, MetaToul Lipidomics, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: chemistry.chemical_classification, Stereochemistry, 010401 analytical chemistry, Organic Chemistry, Clinical Biochemistry, Maleic anhydride, Ketene, Protonation, Glutamic acid, 010402 general chemistry, 01 natural sciences, Biochemistry, Dissociation (chemistry), 0104 chemical sciences, Amino acid, chemistry.chemical_compound, Regioselectivity, chemistry, N-fatty-acyl amino-acid, Amide, Aspartic acid, ESI/MSn, Ion-dipole, [CHIM]Chemical Sciences
Abstract: Lipidomics calls for information on detected lipids and conjugates whose structural elucidation by mass spectrometry requires to rationalization of their gas phase dissociations toward collision-induced dissociation (CID) processes. This study focused on activated dissociations of two lipoamino acid (LAA) systems composed of N-palmitoyl acyl coupled with aspartic and glutamic acid mono ethyl esters (as LAA(*D) and LAA(*E)). Although in MS/MS, their CID spectra show similar trends, e.g., release of water and ethanol, the [(LAA(*D/*E)+H)–C2H5OH]+ product ions dissociate via distinct pathways in sequential MS3 experiments. The formation of all the product ions is rationalized by charge-promoted cleavages often involving stepwise processes with ion isomerization into ion–dipole prior to dissociation. The latter explains the maleic anhydride or ketene neutral losses from N-palmitoyl acyl aspartate and glutamate anhydride fragment ions, respectively. Consequently, protonated palmitoyl acid amide is generated from LAA(*D), whereas LAA(*E) leads to the [*E+H–H2O]+ anhydride. The former releases ammonia to provide acylium, which gives the C n H(2n−1) and C n H(2n−3) carbenium series. This should offer structural information, e.g., to locate either unsaturation(s) or alkyl group branching present on the various fatty acyl moieties of lipo-aspartic acid in further studies based on MS n experiments.
Published: 2016
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112. Hepatic and serum lipid signatures specific to nonalcoholic steatohepatitis in murine models

Author: Catherine Guettier, François Le Naour, Franck Chiappini, Justine Bertrand-Michel, and Christophe Desterke
Subjects: Serum, 0301 basic medicine, Nonalcoholic steatohepatitis, medicine.medical_specialty, Pathology, Cirrhosis, Normal diet, Biostatistics, Biology, Article, Machine Learning, Mice, 03 medical and health sciences, Non-alcoholic Fatty Liver Disease, Internal medicine, medicine, Animals, Multidisciplinary, Fatty liver, Methionine choline deficient diet, nutritional and metabolic diseases, High fat diet, Prognosis, medicine.disease, Lipids, digestive system diseases, Diet, Disease Models, Animal, 030104 developmental biology, Endocrinology, Liver, Hepatocellular carcinoma, lipids (amino acids, peptides, and proteins), Liver pathology
Abstract: Nonalcoholic fatty liver (NAFL) is a precursor of nonalcoholic steatohepatitis (NASH), a condition that may progress to cirrhosis and hepatocellular carcinoma. Markers for diagnosis of NASH are still lacking. We have investigated lipid markers using mouse models that developed NAFL when fed with high fat diet (HFD) or NASH when fed using methionine choline deficient diet (MCDD). We have performed a comprehensive lipidomic analysis on liver tissues as well as on sera from mice fed HFD (n = 5), MCDD (n = 5) or normal diet as controls (n = 10). Machine learning approach based on prediction analysis of microarrays followed by random forests allowed identifying 21 lipids out of 149 in the liver and 14 lipids out of 155 in the serum discriminating mice fed MCDD from HFD or controls. In conclusion, the global approach implemented allowed characterizing lipid signatures specific to NASH in both liver and serum from animal models. This opens new avenue for investigating early and non-invasive lipid markers for diagnosis of NASH in human.
Published: 2016
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113. Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD

Author: Thierry Pineau, Talal Al Saati, Frédéric Lasserre, Edwin Fouché, Justine Bertrand-Michel, Laila Mselli-Lakhal, Alexandra Montagner, Dominique Langin, Fadila Benhamed, Hervé Guillou, Sandrine Lagarrigue, Simon Ducheix, Catherine Postic, Nicolas Loiseau, Céline Lukowicz, Valentin Barquissau, Patricia Cano, Gilles Mithieux, Alison Iroz, Walter Wahli, Marion Régnier, Yannick Lippi, Fabienne Rajas, Arnaud Polizzi, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), Transcriptomic impact of Xenobiotics (E23 TRiX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), U855, Nutrition et cerveau, Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Nanyang Technological University [Singapour], Université de Lausanne (UNIL), Di Carlo, Marie-Ange, Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Université de Lausanne = University of Lausanne (UNIL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UPS), Université Fédérale Toulouse Midi-Pyrénées, UMR 1048 Institute of Metabolic and Cardiovascular Diseases, UMR 1048, Université Paris Descartes - Paris 5 (UPD5), Université Toulouse III - Paul Sabatier (UPS), US006/CREFRE, Centre Hospitalier Universitaire de Purpan (CHU Purpan), U855, Université de Lyon, Université de Brest (UBO), Laboratory of Clinical Biochemistry, Centre Hospitalier Universitaire de Toulouse, Lee Kong Chian School of Medicine, Center for Integrative Genomics, Université de Lausanne, ToxAlim ( ToxAlim ), Institut National Polytechnique [Toulouse] ( INP ) -Institut National de la Recherche Agronomique ( INRA ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse ( ENVT ), Institut National Polytechnique de Toulouse ( INPT ) -Institut National Polytechnique de Toulouse ( INPT ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Toulouse III - Paul Sabatier ( UPS ), Centre Hospitalier Universitaire de Purpan ( CHU Purpan ), Université de Lyon (COMUE), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] ( PEGASE ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, and Université de Brest ( UBO )
Subjects: Male, 0301 basic medicine, Aging, FGF21, [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, Peroxisome proliferator-activated receptor, Hypothermia, métabolisme des lipides, [ SDV.BA ] Life Sciences [q-bio]/Animal biology, Toxicology, chemistry.chemical_compound, 0302 clinical medicine, Cytochrome P-450 Enzyme System, Fenofibrate, glyceride metabolism, liver steatosis, liver function tests, Non-alcoholic Fatty Liver Disease, Adipocyte, Adipocytes, Homeostasis, Fatty acid homeostasis, Hypolipidemic Agents, Mice, Knockout, Animal biology, LIPID METABOLISM, chemistry.chemical_classification, glyceride metabolism, NONALCOHOLIC STEATOHEPATITIS, [SDV.BA]Life Sciences [q-bio]/Animal biology, Fatty Acids, Fatty liver, Gastroenterology, Fasting, foie, Liver, [SDV.TOX]Life Sciences [q-bio]/Toxicology, 030220 oncology & carcinogenesis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], expression des gènes, GENE EXPRESSION, medicine.medical_specialty, Lipolysis, Biology, liver steatosis, 03 medical and health sciences, métabolisme des lipides, expression des gènes, stéatose hépatique, foie, stéatose hépatique, Internal medicine, Biologie animale, medicine, Animals, Humans, PPAR alpha, Cytochrome P450 Family 4, RNA, Messenger, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Triglycerides, Toxicologie, Hepatology, Gene Expression Profiling, Lipid metabolism, Overweight, medicine.disease, Hypoglycemia, Mice, Inbred C57BL, Fibroblast Growth Factors, Disease Models, Animal, 030104 developmental biology, Endocrinology, chemistry, Hepatocytes, MESH: GENE EXPRESSION, liver function tests, Steatosis
Abstract: Supplementary Data : http://gut.bmj.com/content/early/2016/01/31/gutjnl-2015-310798/suppl/DC1; International audience; OBJECTIVE:Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARα on non-alcoholic fatty liver disease (NAFLD).DESIGN:We constructed a novel hepatocyte-specific PPARα knockout (Pparα(hep-/-)) mouse model. Using this novel model, we performed transcriptomic analysis following fenofibrate treatment. Next, we investigated which physiological challenges impact on PPARα. Moreover, we measured the contribution of hepatocytic PPARα activity to whole-body metabolism and fibroblast growth factor 21 production during fasting. Finally, we determined the influence of hepatocyte-specific PPARα deficiency in different models of steatosis and during ageing.RESULTS:Hepatocyte PPARα deletion impaired fatty acid catabolism, resulting in hepatic lipid accumulation during fasting and in two preclinical models of steatosis. Fasting mice showed acute PPARα-dependent hepatocyte activity during early night, with correspondingly increased circulating free fatty acids, which could be further stimulated by adipocyte lipolysis. Fasting led to mild hypoglycaemia and hypothermia in Pparα(hep-/-) mice when compared with Pparα(-/-) mice implying a role of PPARα activity in non-hepatic tissues. In agreement with this observation, Pparα(-/-) mice became overweight during ageing while Pparα(hep-/-) remained lean. However, like Pparα(-/-) mice, Pparα(hep-/-) fed a standard diet developed hepatic steatosis in ageing.CONCLUSIONS:Altogether, these findings underscore the potential of hepatocyte PPARα as a drug target for NAFLD.
Published: 2016
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114. Author response: Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism

Author: Walter Wahli, Nicolas Leuenberger, Chek Kun Tan, Gianpaolo Rando, Hervé Guillou, Nourhène Khaled, Alexandra Montagner, Justine Bertrand-Michel, and Eeswari Paramalingam
Subjects: medicine.medical_specialty, Glucocorticoid receptor, Endocrinology, Catabolism, Fetal mouse, Chemistry, Internal medicine, medicine, Milk lipid
Published: 2016
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115. ATP-binding cassette transporter 1 (ABCA1) deficiency decreases platelet reactivity and reduces thromboxane A2 production independently of hematopoietic ABCA1

Author: Sonia Severin, C. Broccardo, Cédric Garcia, Pierre Sié, Bernard Payrastre, P. Couvert, P. Le Faouder, Béatrice Hechler, Justine Bertrand-Michel, G. Chimini, J. Van Rothem, T. Lhermusier, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Time Factors, Platelet Aggregation, Apolipoprotein B, 030204 cardiovascular system & hematology, Thromboxane A2, chemistry.chemical_compound, 0302 clinical medicine, Tangier disease, polycyclic compounds, Platelet, Tangier Disease, Feedback, Physiological, Mice, Knockout, Hematopoietic Stem Cell Transplantation, hemic and immune systems, Hematology, Middle Aged, Phenotype, Biochemistry, Mice, Inbred DBA, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, ATP Binding Cassette Transporter 1, medicine.drug, Blood Platelets, medicine.medical_specialty, Biology, 03 medical and health sciences, Thrombin, Internal medicine, medicine, Animals, Humans, Genetic Predisposition to Disease, Cell Size, Hemostasis, nutritional and metabolic diseases, Thrombosis, Hematopoietic Stem Cells, medicine.disease, Disease Models, Animal, 030104 developmental biology, Endocrinology, chemistry, ABCA1, biology.protein, Lipoprotein
Abstract: International audience; The role of ATP-binding cassette transporter 1 (ABCA1) in platelet functions is poorly characterized. We studied the impact of ABCA1 deficiency on platelet responses in a mouse model and two Tangier patients. ABCA1-deficient platelets exhibit reduced positive feedback loop mechanisms. This reduced reactivity is dependent on external environment and independent of hematopoietic ABCA1. Summary Background The ATP-binding cassette transporter ABCA1 is required for the conversion of apolipoprotein A-1 to high-density lipoprotein (HDL), and its defect causes Tangier disease, a rare disorder characterized by an absence of HDL and accumulation of cholesterol in peripheral tissues. The role of ABCA1 in platelet functions remains poorly characterized. Objective To determine the role of ABCA1 in platelet functions and to clarify controversies concerning its implication in processes as fundamental as platelet phosphatidylserine exposure and control of platelet membrane lipid composition. Methods and results We studied the impact of ABCA1 deficiency on platelet responses in a mouse model and in two Tangier patients. We show that platelets in ABCA1-deficient mice are slightly larger in size and exhibit aggregation and secretion defects in response to low concentrations of thrombin and collagen. These platelets have normal cholesterol and major phospholipid composition, granule morphology, or calcium-induced phosphatidylserine exposure. Interestingly, ABCA1-deficient platelets display a reduction in positive feedback loop mechanisms, particularly in thromboxane A2 (TXA2) production. Hematopoietic chimera mice demonstrated that defective eicosanoids production, particularly TXA2, was primarily dependent on external environment and not on the hematopoietic ABCA1. Decreased aggregation and production of TXA2 and eicosanoids were also observed in platelets from Tangier patients. Conclusions Absence of ABCA1 and low HDL level induce reduction of platelet reactivity by decreasing positive feedback loops, particularly TXA2 production through a hematopoietic ABCA1-independent mechanism.
Published: 2016
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116. Le récepteur nucléaire LXR est important dans la détoxification de la fumonisine B1

Author: Arnaud Polizzi, P. Goubeyre, Justine Bertrand-Michel, H. Guillou, Nicolas Loiseau, Isabelle P. Oswald, Marion Régnier, Yannick Lippi, and Aude Dupuy
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract: Introduction et but de l’etude La fumonisine B1 est une mycotoxine produite par plusieurs especes de moisissures du genre Fusarium, retrouvees principalement dans le mais et dans le ble. A forte dose, elle entraine une hepatotoxicite et des œdemes pulmonaires chez les animaux. La fumonisine B1 est connue pour etre un inhibiteur pharmacologique de la voie de biosynthese des ceramides, au cœur du metabolisme complexe des sphingolipides. La fumonisine B1 influence l’homeostasie du cholesterol par des mecanismes qui restent a definir. L’objectif de cette etude etait d’evaluer la contribution du liver X receptor (LXR), un recepteur nucleaire qui controle l’elimination du cholesterol par les voies biliaires, dans les effets hepatiques de la fumonisine B1. Materiel et methodes Des souris LXRα/β+/+ et LXRα/β–/–ont recu quotidiennement durant 28 jours differentes doses de fumonisine B1 (0 ; 0,1 ; 1,0 ; 10 mg/kg p.c) dans l’eau de boisson. Les foies ont ete preleves et analyses par des approches biochimiques, histologiques et moleculaires. Resultats En premier lieu, nos resultats montrent que selon la dose administree, la fumonisine B1 avait des effets inverses sur le metabolisme des ceramides. La synthese de ceramide etait augmentee par l’administration d’une faible dose de fumonisine B1 (1 mg/kg/j) alors qu’elle etait diminuee en presence d’une forte dose (10 mg/kg/j). Ces resultats ont ete confirmes par le rapport sphinganine/sphingonine qui diminue a faible dose et qui augmente a forte dose. En second lieu, nos resultats ont demontre que la toxicite hepatique induite par la fumonisine etait sensible a LXR. En effet, a forte dose, la fumonisine B1 entrainait une augmentation des taux plasmatiques d’ASAT, ALAT chez les souris LXRα/β–/–. Histologiquement, les foies de ces memes souris presentaient de nombreux foci inflammatoires a l’inverse des souris WT contaminees avec 10 mg/kg de fumonisine. A forte dose, la fumonisine B1 s’accumulait anormalement dans le plasma des souris LXRα/β–/–. Parallelement, la fumonisine B1 induisait une augmentation significative des differents taux de cholesterols plasmatiques chez les souris LXRα/β–/–. Une analyse par microarray realisee sur les foies de souris LXRα/β+/+ et LXRα/β–/–exposees ou non a la fumonisine B1 a permis de confirmer les effets specifiques de la fumonisine B1 en absence de LXR. En outre, l’analyse des donnees a confirme aussi qu’en absence de LXR, la fumonisine B1 induisait une reponse inflammatoire hepatique. Enfin, nous avons mis en evidence un groupe de genes dont l’expression etait reprimee uniquement chez les souris LXRα/β–/–exposees avec une forte dose de fumonisine B1. C’est le cas de nombreux genes de detoxification (Fmo3, Sult3a1, Cyp2b10) et du metabolisme du cholesterol et des acides biliaires (Abcg8, Cyp7a1, Cyp8b1). Conclusion L’ensemble de ces resultats suggerent que le recepteur nucleaire LXR soit important dans les mecanismes de detoxification hepatique de la fumonisine B1 et que cette detoxification implique une modulation de la synthese et de la degradation du cholesterol en acides biliaires.
Published: 2017
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117. MP252LYSOPHOSPHATIDIC ACID PROTECTS AGAINST ENDOTOXEMIA-ASSOCIATED ACUTE KIDNEY INJURY

Author: Audrey Casemayou, Dimitri Marsal, Koryun Mirzoyan, Justine Bertrand-Michel, Jean-Sébastien Saulnier-Blache, Marion Gillet, Jean-Loup Bascands, and J.P. Schanstra
Subjects: Transplantation, medicine.medical_specialty, Nephrology, business.industry, Internal medicine, medicine, Acute kidney injury, medicine.disease, business, Gastroenterology
Published: 2017
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118. Proteolipidic Composition of Exosomes Changes during Reticulocyte Maturation

Author: Laurence Salomé, Stéphanie Balor, Elsa Ronzier, Etienne Joly, Justine Bertrand-Michel, André Lopez, Karima Chaoui, François Tercé, Ikrame Lazar, Véronique Roques, and Kévin Carayon
Subjects: Male, Proteomics, Reticulocytes, Endosome, Cellular differentiation, Membrane lipids, Endosomes, Biology, Biochemistry, Rats, Sprague-Dawley, Hemoglobins, Membrane Lipids, Reticulocyte, medicine, Animals, Molecular Biology, Membrane Proteins, Cell Differentiation, Cell Biology, Microvesicles, Rats, Cell biology, medicine.anatomical_structure, Membrane protein, Biogenesis
Abstract: During the orchestrated process leading to mature erythrocytes, reticulocytes must synthesize large amounts of hemoglobin, while eliminating numerous cellular components. Exosomes are small secreted vesicles that play an important role in this process of specific elimination. To understand the mechanisms of proteolipidic sorting leading to their biogenesis, we have explored changes in the composition of exosomes released by reticulocytes during their differentiation, in parallel to their physical properties. By combining proteomic and lipidomic approaches, we found dramatic alterations in the composition of the exosomes retrieved over the course of a 7-day in vitro differentiation protocol. Our data support a previously proposed model, whereby in reticulocytes the biogenesis of exosomes involves several distinct mechanisms for the preferential recruitment of particular proteins and lipids and suggest that the respective prominence of those pathways changes over the course of the differentiation process.
Published: 2011
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119. Deletion of Stearoyl-CoA Desaturase-1 From the Intestinal Epithelium Promotes Inflammation and Tumorigenesis, Reversed by Dietary Oleate

Author: Antonio Moschetta, Simon Ducheix, Carla Frau, Carlo Sabbà, Marcello Chieppa, Gabriele Mocciaro, Justine Bertrand-Michel, Jennifer Härdfeldt, Michelina Plateroti, Jean-Marc A. Lobaccaro, Stefania De Santis, Julian L. Griffin, James M. Ntambi, Claudia Peres, Elena Piccinin, Ducheix, S., Peres, C., Hardfeldt, J., Frau, C., Mocciaro, G., Piccinin, E., Lobaccaro, J. -M., De Santis, S., Chieppa, M., Bertrand-Michel, J., Plateroti, M., Griffin, J. L., Sabba, C., Ntambi, J. M., and Moschetta, A.
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dietary Fats, Unsaturated, Internal medicine, Intestinal Neoplasms, medicine, Animals, Intestinal Mucosa, Fatty acid homeostasis, Colorectal, chemistry.chemical_classification, Mouse Model, Colon Cancer, Hepatology, Chemistry, Azoxymethane, Gastroenterology, Intestinal epithelium, Enteritis, Tumor Burden, Monounsaturated, Mice, Inbred C57BL, Oleic acid, 030104 developmental biology, Endocrinology, Enzyme, Real-time polymerase chain reaction, 030220 oncology & carcinogenesis, Female, lipids (amino acids, peptides, and proteins), Tumor necrosis factor alpha, Stearoyl-CoA desaturase-1, Stearoyl-CoA Desaturase, Oleic Acid
Abstract: Background & Aims The enzyme stearoyl-coenzyme A desaturase 1 (SCD or SCD1) produces monounsaturated fatty acids by introducing double bonds into saturated bonds between carbons 9 and 10, with oleic acid as the main product. SCD1 is present in the intestinal epithelium, and fatty acids regulate cell proliferation, so we investigated the effects of SCD1-induced production of oleic acid in enterocytes in mice. Methods We generated mice with disruption of Scd1 selectively in the intestinal epithelium (iScd1–/– mice) on a C57BL/6 background; iScd1+/+ mice were used as controls. We also generated iScd1–/–ApcMin/+ mice and studied cancer susceptibility. Mice were fed a chow, oleic acid–deficient, or oleic acid–rich diet. Intestinal tissues were collected and analyzed by histology, reverse transcription quantitative polymerase chain reaction, immunohistochemistry, and mass spectrometry, and tumors were quantified and measured. Results Compared with control mice, the ileal mucosa of iScd1–/– mice had a lower proportion of palmitoleic (C16:1 n-7) and oleic acids (C18:1 n-9), with accumulation of stearic acid (C18:0); this resulted a reduction of the Δ9 desaturation ratio between monounsaturated (C16:1 n-7 and C18:1 n-9) and saturated (C16:0 and C18:0) fatty acids. Ileal tissues from iScd1–/– mice had increased expression of markers of inflammation activation and crypt proliferative genes compared with control mice. The iScd1–/– ApcMin/+ mice developed more and larger tumors than iScd1+/+ApcMin/+ mice. iScd1–/–ApcMin/+ mice fed the oleic acid-rich diet had reduced intestinal inflammation and significantly lower tumor burden compared with mice fed a chow diet. Conclusions In studies of mice, we found intestinal SCD1 to be required for synthesis of oleate in the enterocytes and maintenance of fatty acid homeostasis. Dietary supplementation with oleic acid reduces intestinal inflammation and tumor development in mice.
Published: 2018
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120. Ablation of the very‐long‐chain fatty acid elongase ELOVL3 in mice leads to constrained lipid storage and resistance to diet‐induced obesity

Author: Justine Bertrand-Michel, Mats Rudling, Hervé Guillou, Annelie Brolinson, C. Carneheim, Robert I. Csikasz, Jan Borén, Rachel M. Fisher, Anders Jacobsson, Damir Zadravec, Stockholm University, Karolinska Institutet [Stockholm], CHU Toulouse [Toulouse], Sahlgrenska University Hospital [Gothenburg], Unité de recherche Pharmacologie-Toxicologie (UPT), Institut National de la Recherche Agronomique (INRA), Swedish Research Council, and INRA and Formas
Subjects: Male, obesity, LIVER, [SDV]Life Sciences [q-bio], PROTEIN, Lipoproteins, VLDL, Biochemistry, DEFICIENT MICE, Eating, Mice, chemistry.chemical_compound, 0302 clinical medicine, gender, Cells, Cultured, Mice, Knockout, 2. Zero hunger, INSULIN-RESISTANCE, 0303 health sciences, Elongase, BROWN ADIPOSE-TISSUE, Adipose Tissue, 030220 oncology & carcinogenesis, Female, Adiponectin, BETA-OXIDATION, Biotechnology, medicine.medical_specialty, RAT-HEART, Fatty Acid Elongases, Very long chain fatty acid, METABOLISM, Biology, Lipid storage, Gene Expression Regulation, Enzymologic, 03 medical and health sciences, Sex Factors, VLCFA, LEPTIN, Adipokines, Acetyltransferases, Internal medicine, Genetics, medicine, Animals, adipocyte protein 2, Molecular Biology, Triglycerides, Fatty acid synthesis, fatty acid synthesis, 030304 developmental biology, Lipogenesis, Lipid metabolism, medicine.disease, Obesity, Diet, Mice, Inbred C57BL, Endocrinology, chemistry, Heart failure, biology.protein, GLUCOSE-HOMEOSTASIS, Basal Metabolism
Abstract: International audience; Although saturated and monounsaturated very-long-chain fatty acids (VLCFAs) have long been associated with undesirable effects on health, including obesity, heart failure, and atherosclerosis, the physiological role of endogenous synthesis is largely unknown. The fatty acid elongase ELOVL3 is involved in the synthesis of C20-C24 saturated and monounsaturated VLCFAs mainly in liver, brown and white adipose tissue, and triglyceride-rich glands such as the sebaceous and meibomian glands. Here we show that ablation of ELOVL3 leads to reduced adiponectin levels, constrained expansion of adipose tissue, and resistance against diet-induced obesity, a situation that is more exaggerated in female mice. Both female and male knockout mice show reduced hepatic lipogenic gene expression and triglyceride content, a situation that is associated with reduced de novo fatty acid synthesis and uptake. As a consequence, the VLDL-triglyceride level in serum is significantly reduced. Remarkably, despite increased energy expenditure, markedly reduced serum levels of leptin, and increased expression of orexigenic peptides in the hypothalamus, the Elovl3(-/-) mice do not compensate by increased food intake. Thus, these results reveal that C20-C22 saturated and monounsaturated VLCFAs produced by ELOVL3 are indispensable for appropriate synthesis of liver triglycerides, fatty acid uptake, and storage in adipose tissue.-Zadravec, D., Brolinson, A., Fisher, R. M., Carneheim, C., Csikasz, R. I., Bertrand-Michel, J., Boren, J., Guillou, H., Rudling, M., Jacobsson, A. Ablation of the very-long-chain fatty acid elongase ELOVL3 in mice leads to constrained lipid storage and resistance to diet-induced obesity. FASEB J. 24, 4366-4377 (2010). www.fasebj.org
Published: 2010
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121. Glutathione transferases kappa 1 and kappa 2 localize in peroxisomes and mitochondria, respectively, and are involved in lipid metabolism and respiration in Caenorhabditis elegans

Author: Fabrice Morel, Elise Petit, Xavier Michelet, Renaud Legouis, Claudine Rauch, François Tercé, and Justine Bertrand-Michel
Subjects: Gene knockdown, biology, Lipid metabolism, Cell Biology, Mitochondrion, Peroxisome, biology.organism_classification, Biochemistry, RNA interference, Gene expression, Molecular Biology, Gene, Caenorhabditis elegans
Abstract: To elucidate the function of kappa class glutathione transferases (GSTs) in multicellular organisms, their expression and silencing were investigated in Caenorhabditis elegans. In contrast with most vertebrates, which possess only one GST kappa gene, two distinct genes encoding GSTK-1 and GSTK-2 are present in the C. elegans genome. The amino acid sequences of GSTK-1 and GSTK-2 share around 30% similarity with the human hGSTK1 sequence and, like the human transferase, GSTK-1 contains a C-terminal peroxisomal targeting sequence. gstk-1 and gstk-2 genes show distinct developmental and tissue expression patterns. We show that GSTK-2 is localized in the mitochondria and expressed mainly in the pharynx, muscles and epidermis, whereas GSTK-1 is restricted to peroxisomes and expressed in the intestine, body wall muscles and epidermis. In order to determine the potential role(s) of GST kappa genes in C. elegans, specific silencing of the gstk-1 and gstk-2 genes was performed by an RNA interference approach. Knockdown of gstk-1 or gstk-2 had no apparent effect on C. elegans reproduction, development, locomotion or lifespan. By contrast, when biological functions (oxygen consumption and lipid metabolism) related to peroxisomes and/or mitochondria were investigated, we observed a significant decrease in respiration rate and a lower concentration of the monounsaturated fatty acid cis-vaccenic acid (18:1omega7) when worms were fed on bacteria expressing RNA interference targeting both gstk-1 and gstk-2. These results demonstrate that GST kappa, although not essential for the worm's life, may be involved in energetic and lipid metabolism, two functions related to mitochondria and peroxisomes.
Published: 2009
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122. Sterol metabolism in the oomycete Aphanomyces euteiches , a legume root pathogen

Author: Elodie Gaulin, Justine Bertrand-Michel, Bernard Dumas, and Mohammed-Amine Madoui
Subjects: Oomycete, Physiology, Plant Science, Biology, biology.organism_classification, Sterol, Microbiology, Brown algae, Metabolic pathway, Biochemistry, Phylogenetics, polycyclic compounds, biology.protein, Demethylase, lipids (amino acids, peptides, and proteins), Aphanomyces euteiches, Fucosterol
Abstract: Summary • Sterols are isoprenoid-derived molecules that have essential functions in eukaryotes but whose metabolism remains largely unknown in a large number of organisms. Oomycetes are fungus-like microorganisms that are evolutionarily related to stramenopile algae, a large group of organisms for which no sterol metabolic pathway has been reported. Here, we present data that support a model of sterol biosynthesis in Aphanomyces euteiches, an oomycete species causing devastating diseases in legume crops. • In silico analyses were performed to identify genes encoding enzymes involved in the conversion of the isoprenoid precursor 3-hydroxy-3-methylglutaryl coenzyme A to isoprenoids. Several metabolic intermediates and two major sterol end-products were identified by gas chromatography–mass spectroscopy. • We show that A. euteiches is able to produce fucosterol (a sterol initially identified in brown algae) and cholesterol (the major animal sterol). Mycelium development is inhibited by two sterol demethylase inhibitors used as fungicides, namely tebuconazole and epoxiconazole. • We propose the first sterol biosynthetic pathway identified in a stramenopile species. Phylogenetic analyses revealed close relationships between A. euteiches enzyme sequences and those found in stramenopile algae, suggesting that part of this pathway could be conserved in the Stramenopila kingdom.
Published: 2009
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123. Atypical cleavage of protonated N-fatty acyl amino acids derived from aspartic acid evidenced by sequential MS

Author: Toufik Taalibi, Boukerche, Sandra, Alves, Pauline, Le Faouder, Anna, Warnet, Justine, Bertrand-Michel, Mohamed, Bouchekara, Mohammed, Belbachir, and Jean-Claude, Tabet
Subjects: Ions, Aspartic Acid, Ethyl Ethers, Tandem Mass Spectrometry, Glutamic Acid, Water, Hydrogenation, Lipids, Anhydrides
Abstract: Lipidomics calls for information on detected lipids and conjugates whose structural elucidation by mass spectrometry requires to rationalization of their gas phase dissociations toward collision-induced dissociation (CID) processes. This study focused on activated dissociations of two lipoamino acid (LAA) systems composed of N-palmitoyl acyl coupled with aspartic and glutamic acid mono ethyl esters (as LAA
Published: 2016

124. Oleate dose-dependently regulates palmitate metabolism and insulin signaling in C2C12 myotubes

Author: Cécile Acquaviva, Béatrice Morio, Naoufel Cheraiti, Frédéric Capel, Carina Prip-Buus, Justine Bertrand-Michel, Carole Hénique, Christine Vianey-Saban, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Service maladies héréditaires du métabolisme, Centre de Biologie et pathologie Est, Centre Hospitalier Universitaire de Lyon, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Service de Maladies Héréditaires du Métabolisme, Centre de Biologie Et de Pathologie Est - Bron Centre médical, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), UMR 1048-12MC, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), MetaToul Lipidomics, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul-Lipidomique, MetaboHUB, Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Clermont Auvergne (UCA)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Muscle Fibers, Skeletal, Palmitates, Skeletal muscle, p38 Mitogen-Activated Protein Kinases, Mice, chemistry.chemical_compound, Insulin, Phosphorylation, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, acide gras, Fatty Acids, beta oxydation, NF-kappa B, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, insulino- résistance, Insulin signaling, medicine.anatomical_structure, 2 oxidation, Lipotoxicity, Oxidation-Reduction, Signal Transduction, medicine.medical_specialty, Ceramide, Biology, Substrate partitioning, Ceramides, Cell Line, Diglycerides, 03 medical and health sciences, Insulin resistance, Carnitine, Internal medicine, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Muscle, Skeletal, Molecular Biology, Triglycerides, Fatty acid, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Metabolism, medicine.disease, Insulin receptor, 030104 developmental biology, Endocrinology, Lipid metabolism, chemistry, biology.protein, myotube, fatty acid, Insulin Resistance, Proto-Oncogene Proteins c-akt, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Oleic Acid
Abstract: The work was supported by the authors' institutions, INRA and Cochin Institute; Because the protective effect of oleate against palmitate-induced insulin resistance may be lessened in skeletal muscle once cell metabolism is overloaded by fatty acids (FAs), we examined the impact of varying amounts of oleate on palmitate metabolic channeling and insulin signaling in C2C12 myotubes. Cells were exposed to 05 mM of palmitate and to increasing doses of oleate (0.05, 025 and 0.5 mM). Impacts of FA treatments on radio-labelled FA fluxes, on cellular content in diacylglycerols (DAG), triacylglycerols (TAG), ceramides, acylcarnitines, on PKC theta, MAPKs (ERK1/2, p38) and NF-KB activation, and on insulin-dependent Akt phosphorylation were examined. Low dose of oleate (0.05 mM) was sufficient to improve palmitate complete oxidation to CO2 (+29%, P< 0.05) and to alter the cellular acylcarnitine profile. Insulin-induced Ala phosphorylation was 48% higher in that condition vs. palmitate alone (p < 0.01). Although DAG and ceramide contents were significantly decreased with 0.05 mM of oleate vs. palmitate alone (-47 and -28%, respectively, p < 0.01), 0.25 mM of oleate was required to decrease p38 MAPK and PKC theta phosphorylation, thus further improving the insulin signaling (+32%, p < 0.05). By contrast, increasing oleate concentration from 025 to 05 mM, thus increasing total amount of FA from 0.75 to 1 mM, deteriorated the insulin signaling pathway (-30%, p < 0.01). This was observed despite low contents in DAG and ceramides, and enhanced palmitate incorporation into TAG (+ 27%, p < 0.05). This was associated with increased incomplete FA beta-oxidation and impairment of acylcarnitine profile. In conclusion, these combined data place mitochondrial beta-oxidation at the center of the regulation of muscle insulin sensitivity, besides p38 MAPK and PKC theta
Published: 2016
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125. Glucocorticoid receptor-PPAR alpha axis in fetal mouse liver prepares neonates for milk lipid catabolism

Author: Eeswari Paramalingam, Chek Kun Tan, Nicolas Leuenberger, Alexandra Montagner, Nourhène Khaled, Justine Bertrand-Michel, Hervé Guillou, Walter Wahli, Gianpaolo Rando, Center for Integrative Genomics, Université de Lausanne, Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Plateforme Metatoul, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherche 150 - Bio-Médicale de Toulouse, Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung, Nanyang Technological University, Bonizzi-Theler Stiftung, Human Frontier Science Program, 7th EU Program TORNADO, Pôle de Recherche National 'Frontiers in Genetics', Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Nanyang Technological University (NTU), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), ProdInra, Archive Ouverte, Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), MetaboHUB-MetaToul, Institut Fédératif de Recherche Bio-médicale Institution (IFR150), and Lee Kong Chian School of Medicine (LKCMedicine)
Subjects: 0301 basic medicine, FGF21, récepteur ppar, Mouse, [SDV]Life Sciences [q-bio], Peroxisome proliferator-activated receptor, souris, newborn animal, PPARα, 0302 clinical medicine, Glucocorticoid receptor, pparalpha, glucocorticoid receptor, catabolisme lipidique, Biology (General), chemistry.chemical_classification, General Neuroscience, hepatic steatosis, Gene Expression Regulation, Developmental, General Medicine, foie, ketone body, [SDV] Life Sciences [q-bio], Milk, Liver, Medicine, Energy source, Research Article, medicine.medical_specialty, mice, QH301-705.5, Science, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Receptors, Glucocorticoid, activation de la transcription, Internal medicine, medicine, Animals, PPAR alpha, Epigenetics, Fetus, General Immunology and Microbiology, Catabolism, lipid catabolism, HDAC3, nouveau né, Lipid metabolism, Lipid Metabolism, 030104 developmental biology, Endocrinology, Developmental Biology and Stem Cells, Metabolism, chemistry, liver function tests, Energy Metabolism, 030217 neurology & neurosurgery
Abstract: In mammals, hepatic lipid catabolism is essential for the newborns to efficiently use milk fat as an energy source. However, it is unclear how this critical trait is acquired and regulated. We demonstrate that under the control of PPARα, the genes required for lipid catabolism are transcribed before birth so that the neonatal liver has a prompt capacity to extract energy from milk upon suckling. The mechanism involves a fetal glucocorticoid receptor (GR)-PPARα axis in which GR directly regulates the transcriptional activation of PPARα by binding to its promoter. Certain PPARα target genes such as Fgf21 remain repressed in the fetal liver and become PPARα responsive after birth following an epigenetic switch triggered by β-hydroxybutyrate-mediated inhibition of HDAC3. This study identifies an endocrine developmental axis in which fetal GR primes the activity of PPARα in anticipation of the sudden shifts in postnatal nutrient source and metabolic demands. DOI: http://dx.doi.org/10.7554/eLife.11853.001, eLife digest Birth is a highly stressful and critical event. In the womb, babies rely on the supply of oxygen and nutrients provided by the placenta. However, once they are born they need to breathe for themselves and gain all their nutrients from suckling milk. The placenta provides a sugar-rich diet, while milk is richer in fat. Failing to cope with this change in diet leads to serious complications and sometimes death. Therefore, a better understanding of how the body adapts to these changes may shed light on pathways that are important for good health in later life. The liver plays a central role in processing the nutrients absorbed by the gut. It uses fats to produce molecules called ketone bodies, such as β-hydroxybutyrate, which are then used as fuel by other tissues and organs including the heart, muscle and the brain. A protein called PPARα controls the production of ketone bodies primarily by regulating genes that are involved in the uptake and breakdown of fat in the liver. However, little is known about how this protein affects the development of the liver. Here, Rando, Tan et al. report that mice start to produce more PPARα in the liver shortly before birth. This ultimately activates several genes that encode enzymes that break down fats. The experiments show that during labor, stress hormones called glucocorticoids directly stimulate the production of PPARα in the liver of the fetus to prepare newborn mice for harnessing energy from fat-rich milk. In the absence of PPARα, mouse liver cells are less able to break down fats after birth and so start to accumulate fat, resulting in fewer ketone bodies being produced. Rando, Tan et al. show that β-hydroxybutyrate regulates some PPARα target genes, including one called Fgf21. The activity of this gene increases only after milk suckling starts and it encodes a protein that enhances the breakdown of fats in the liver. Without PPARα, the expression levels of its target genes, including Fgf21, do not increase after birth, which promotes the build up of fats in liver cells, a condition known as liver steatosis. Overall, the results reported by Rando, Tan et al. highlight how stress during labor plays an important role in priming the body to cope with a fat-rich diet after birth. Future studies will need to determine if stress hormones and ketone bodies could be used as therapies for babies born by caesarean section with liver steatosis. DOI: http://dx.doi.org/10.7554/eLife.11853.002
Published: 2016
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126. Novel role for carbohydrate responsive element binding protein in the control of ethanol metabolism and susceptibility to binge drinking

Author: Renaud Dentin, Jean Girard, Sophie Lotersztajn, Justine Bertrand-Michel, Catherine Postic, Martine Daujat-Chavanieu, Solenne Marmier, Sabine Gerbal-Chaloin, Hervé Guillou, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), ANR [ANR-09-GENO-011-HEPACOL, ANR-09-JCJC-057-01], Fondation Francaise de la Recherche Medicale (Labelisation Equipe), Ville de Paris, European Commission, and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Context (language use), Resveratrol, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Ethanol metabolism, Carbohydrate-responsive element-binding protein, Fatty acid synthesis, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Alcohol dehydrogenase, 0303 health sciences, Hepatology, biology, Sirtuin 1, medicine.disease, 3. Good health, Endocrinology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Steatosis
Abstract: International audience; Carbohydrate responsive element binding protein (ChREBP) is central for de novo fatty acid synthesis under physiological conditions and in the context of nonalcoholic fatty liver disease. We explored its contribution to alcohol-induced steatosis in a mouse model of binge drinking as acute ethanol (EtOH) intoxication has become an alarming health problem. Within 6 hours, ChREBP acetylation and its recruitment onto target gene promoters were increased in liver of EtOH-fed mice. Acetylation of ChREBP was dependent on alcohol metabolism because inhibition of alcohol dehydrogenase (ADH) activity blunted ChREBP EtOH-induced acetylation in mouse hepatocytes. Transfection of an acetylation-defective mutant of ChREBP (ChREBP(K672A)) in HepG2 cells impaired the stimulatory effect of EtOH on ChREBP activity. Importantly, ChREBP silencing in the liver of EtOH-fed mice prevented alcohol-induced triglyceride accumulation through an inhibition of the lipogenic pathway but also led, unexpectedly, to hypothermia, increased blood acetaldehyde concentrations, and enhanced lethality. This phenotype was associated with impaired hepatic EtOH metabolism as a consequence of reduced ADH activity. While the expression and activity of the NAD(+) dependent deacetylase sirtuin 1, a ChREBP-negative target, were down-regulated in the liver of alcohol-fed mice, they were restored to control levels upon ChREBP silencing. In turn, ADH acetylation was reduced, suggesting that ChREBP regulates EtOH metabolism and ADH activity through its direct control of sirtuin 1 expression. Indeed, when sirtuin 1 activity was rescued by resveratrol pretreatment in EtOH-treated hepatocytes, a significant decrease in ADH protein content and/or acetylation was observed. Conclusion: our study describes a novel role for ChREBP in EtOH metabolism and unravels its protective effect against severe intoxication in response to binge drinking. (Hepatology 2015;62:1086-1100)
Published: 2015
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127. Quantification and Potential Functions of Endogenous Agonists of Transient Receptor Potential Channels in Patients With Irritable Bowel Syndrome

Author: Corinne Rolland, Nicholas A. Veldhuis, Jessica Bertrand, Daniel P. Poole, Pauline Le Faouder, Nicolas Cenac, Nathalie Vergnolle, Lisa Zecchi, Tereza Bautzova, Vincenzo Stanghellini, Wolfgang Liedtke, Marc Dubourdeau, Justine Bertrand-Michel, Nigel W. Bunnett, Giovanni Barbara, Cenac, Nicola, Bautzova, Tereza, Le Faouder, Pauline, Veldhuis, Nicholas A, Poole, Daniel P, Rolland, Corinne, Bertrand, Jessica, Liedtke, Wolfgang, Dubourdeau, Marc, Bertrand-Michel, Justine, Zecchi, Lisa, Stanghellini, Vincenzo, Bunnett, Nigel W, Barbara, Giovanni, and Vergnolle, Nathalie
Subjects: Male, Leukotriene B4, Calcium Channels/metabolism, Biopsy, Nerve Tissue Proteins/metabolism, Colon/cytology/innervation/metabolism, Sensory Receptor Cell, Irritable Bowel Syndrome, chemistry.chemical_compound, Mice, Tandem Mass Spectrometry, Ganglia, Spinal, Irritable Bowel Syndrome/metabolism, Proteolytic Activity, RNA, Small Interfering, Receptor, Irritable bowel syndrome, RNA, Small Interfering/genetics, medicine.diagnostic_test, biology, TRPV Cation Channel, Gastroenterology, Middle Aged, PAR2, Italy, Fatty Acids, Unsaturated, lipids (amino acids, peptides, and proteins), Arachidonic acid, Female, Sensory Receptor Cells/cytology/metabolism, TRPV Cation Channels/metabolism, Human, Signal Transduction, Epoxygenase, Adult, medicine.medical_specialty, Colon, TRPV1, Pain, Calcium Channel, Dinoprostone, Young Adult, Internal medicine, medicine, Transient Receptor Potential Channels/metabolism, Transient Receptor Potential Channel, Animals, Humans, Prostaglandin a, Aged, Hepatology, Animal, business.industry, medicine.disease, Protease, Fatty Acids, Unsaturated/metabolism, Mice, Inbred C57BL, Endocrinology, chemistry, Nerve Tissue Protein, biology.protein, Ganglia, Spinal/cytology/metabolism, Dinoprostone/metabolism, business, Chromatography, Liquid
Abstract: Background & Aims In mice, activation of the transient receptor potential cation channels (TRP) TRPV1, TRPV4, and TRPA1 causes visceral hypersensitivity. These receptors and their agonists might be involved in development of irritable bowel syndrome (IBS). We investigated whether polyunsaturated fatty acid (PUFA) metabolites, which activate TRPs, are present in colon tissues from patients with IBS and act as endogenous agonists to induce hypersensitivity. Methods We analyzed colon biopsy samples from 40 patients with IBS (IBS biopsies) and 11 healthy individuals undergoing colorectal cancer screening (controls), collected during colonoscopy at the University of Bologna, Italy. Levels of the PUFA metabolites that activate TRPV1 (12-hydroperoxyeicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid, 5-hydroxyeicosatetraenoic acid, and leukotriene B4), TRPV4 (5,6-epoxyeicosatrienoic acid [EET] and 8,9-EET), and TRPA1 (PGA 1 , 8-iso-prostaglandin A 2 , and 15-deoxy-Δ-prostaglandin J 2 ) were measured in biopsies and their supernatants using liquid chromatography and tandem mass spectrometry; we also measured levels of the PUFA metabolites prostaglandin E 2 (PGE 2 ) and resolvins. C57Bl6 mice were given intrathecal injections of small interfering RNAs to reduce levels of TRPV4, or control small interfering RNAs, along with colonic injections of biopsy supernatants; visceral hypersensitivity was measured based on response to colorectal distension. Mouse sensory neurons were cultured and incubated with biopsy supernatants and lipids extracted from biopsies or colons of mice. Immunohistochemistry was used to detect TRPV4 in human dorsal root ganglia samples (from the National Disease Research Interchange). Results Levels of the TRPV4 agonist 5,6-EET, but not levels of TRPV1 or TRPA1 agonists, were increased in IBS biopsies compared with controls; increases correlated with pain and bloating scores. Supernatants from IBS biopsies, but not from controls, induced visceral hypersensitivity in mice. Small interfering RNA knockdown of TRPV4 in mouse primary afferent neurons inhibited the hypersensitivity caused by supernatants from IBS biopsies. Levels of 5,6-EET and 15-HETE were increased in colons of mice with, but not without, visceral hypersensitivity. PUFA metabolites extracted from IBS biopsies or colons of mice with visceral hypersensitivity activated mouse sensory neurons in vitro, by activating TRPV4. Mouse sensory neurons exposed to supernatants from IBS biopsies produced 5,6-EET via a mechanism that involved the proteinase-activated receptor-2 and cytochrome epoxygenase. In human dorsal root ganglia, TPV4 was expressed by 35% of neurons. Conclusions Colon tissues from patients with IBS have increased levels of specific PUFA metabolites. These stimulate sensory neurons from mice and generate visceral hypersensitivity via activation of TRPV4.
Published: 2015

128. Validated routine-ready UHPLC/MS-MS method for the reference range determination in human plasma of 15-f2t-isoprostane, biomarker of the oxidative stress

Author: Thomas Dubrowski, Aude Dupuy, Claire Vigor, Thierry Durand, Joël Pincemail, Anne-Françoise Donneau, Jean-Olivier Defraigne, Jean Claude Van Heugen, Justine Bertrand-Michel, Patrice Chiap, and Corinne Charlier
Subjects: 0301 basic medicine, 15-F2t-isoprostane, education.field_of_study, Chromatography, Chemistry, Population, Reference range, Gold standard (test), medicine.disease_cause, Biochemistry, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, In vivo, Physiology (medical), medicine, Biomarker (medicine), education, Oxidative stress
Abstract: Background Isoprostanes are considered as being "gold standard" markers of lipid peroxidation although large differences have been observed in normal plasma reference values. Material and Methods After blood collection on EDTA, plasma samples were purified through an original solid-liquid extraction protocol. After evaporation to dryness and reconstitution, samples were directly injected into an UHPLC/MS-MS system for 15-F2t-isoprostane analysis. Results A population of 61 subjects aged between 18 and 60 years (29 men and 32 women) was selected in our study *. The mean value in plasma 15-F2t-isoprostane obtained was 260 pg / mL with a standard deviation of 55 pg / mL (minimum and maximum values of 294.7 and 403.3 pg / mL). The normal distribution observed gave a reference interval between 151.96 and 368.16 pg/mL. This observation was confirmed by the Shapiro-Wilk test result (p=0.1125). Interestingly, we have observed a moderate but significant positive correlation with the copper/zinc ratio (r=0.34; p=0.01) and a moderate but significant negative correlation with total glutathione (r=- 0.28; p=0.34), both markers being considered as reflecting the presence of in vivo oxidative stress. Conclusion Our study has allowed to measure plasma 15-F2t-isoprostane in a routine way.
Published: 2017
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129. Rôle spécifique de la PI3kinase alpha hépatocytaire : influence sur le diabète et la stéatose hépatique

Author: Arnaud Polizzi, Catherine Postic, Marion Régnier, Frédéric Lasserre, Céline Lukowicz, Alexandra Montagner, Yannick Lippi, Julie Guillermet, Hervé Guillou, Justine Bertrand-Michel, Edwin Fouché, and Nicolas Loiseau
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Published: 2017
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130. Non-enzymatic lipid oxidation products in biological systems:Assessment of the metabolites from polyunsaturated fatty acids

Author: Pauline Le Faouder, Jean-Marie Galano, Claire Vigor, Justine Bertrand-Michel, Joseph Vercauteren, Jetty Chung-Yung Lee, Thierry Durand, Edith Pinot, Camille Oger, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), School of biological sciences (Hong Kong, Chine), The University of Hong Kong (HKU), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, and Heritier, Patrice
Subjects: Clinical Biochemistry, Lipid peroxidation, Isoprostanes, medicine.disease_cause, 01 natural sciences, Biochemistry, Gas Chromatography-Mass Spectrometry, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Lipid oxidation, Tandem Mass Spectrometry, medicine, Animals, Humans, LC-MS/MS, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Chromatography, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010401 analytical chemistry, Fatty acid, Cell Biology, General Medicine, BSTFA, [CHIM.ORGA] Chemical Sciences/Organic chemistry, 0104 chemical sciences, chemistry, Oxidative stress, Fatty Acids, Unsaturated, Gas chromatography–mass spectrometry, GC-MS, Oxidation-Reduction, Chromatography, Liquid, Polyunsaturated fatty acid
Abstract: International audience; Metabolites of non-enzymatic lipid peroxidation of polyunsaturated fatty acids notably omega-3 andomega-6 fatty acids have become important biomarkers of lipid products. Especially the arachidonicacid-derived F2-isoprostanes are the classic in vivo biomarker for oxidative stress in biological systems.In recent years other isoprostanes from eicosapentaenoic, docosahexaenoic, adrenic and -linolenicacids have been evaluated, namely F3-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes and F1-phytoprostanes, respectively. These have been gaining interest as complementary specific biomarkersin human diseases. Refined extraction methods, robust analysis and elucidation of chemical structureshave improved the sensitivity of detection in biological tissues and fluids. Previously the main reliableinstrumentation for measurement was gas chromatography-mass spectrometry (GC-MS), but now theuse of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunological techniquesis gaining much attention. In this review, the types of prostanoids generated from non-enzymatic lipidperoxidation of some important omega-3 and omega-6 fatty acids and biological samples that have beendetermined by GC-MS and LC-MS/MS are discussed.
Published: 2014
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131. Phosphoinositide substrates of myotubularin affect voltage-activated Ca(2)(+) release in skeletal muscle

Author: Estela González Rodríguez, János Vincze, Anna Buj-Bello, Claude Legrand, Romain Lefebvre, Vincent Jacquemond, Karine Poulard, László Csernoch, Péter Szentesi, Dóra Bodnár, Justine Bertrand-Michel, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Physiology, Health Sciences Centre, University of Debrecen, Immunologie moléculaire et biothérapies innovantes (IMBI), Généthon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Évry-Val-d'Essonne (UEVE)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Physiologie intégrative, cellulaire et moléculaire (PICM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratorio de Nanotecnología Molecular (NANOMOL), Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Debrecen Egyetem [Debrecen], École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Physiology, Myotubularin, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Phosphatase, Biology, Fisiología, 03 medical and health sciences, chemistry.chemical_compound, Excitation–contraction coupling, 0302 clinical medicine, Physiology (medical), Internal medicine, Calcium homeostasis, medicine, Elméleti orvostudományok, Phosphatidylinositol, Phosphatidylinositol phosphate, 030304 developmental biology, Calcium metabolism, Sarcoplasmic reticulum Ca2+ release, 0303 health sciences, Ryanodine receptor, Skeletal muscle, Orvostudományok, Endocrinology, medicine.anatomical_structure, chemistry, Biophysics, Phosphorylation, 030217 neurology & neurosurgery, Intracellular
Abstract: Skeletal muscle excitation–contraction (E–C) coupling is altered in several models of phosphatidylinositol phosphate (PtdInsP) phosphatase deficiency and ryanodine receptor activity measured in vitro was reported to be affected by certain PtdInsPs, thus prompting investigation of the physiological role of PtdInsPs in E–C coupling. We measured intracellular Ca2+ transients in voltage-clamped mouse muscle fibres microinjected with a solution containing a PtdInsP substrate (PtdIns(3,5)P 2 or PtdIns(3)P) or product (PtdIns(5)P or PtdIns) of the myotubularin phosphatase MTM1. No significant change was observed in the presence of either PtdIns(5)P or PtdIns but peak SR Ca2+ release was depressed by ~30% and 50% in fibres injected with PtdIns(3,5)P 2 and PtdIns(3)P, respectively, with no concurrent alteration in the membrane current signals associated with the DHPR function as well as in the voltage dependence of Ca2+ release inactivation. In permeabilized muscle fibres, the frequency of spontaneous Ca2+ release events was depressed in the presence of the three tested phosphorylated forms of PtdInsP with PtdIns(3,5)P 2 being the most effective, leading to an almost complete disappearance of Ca2+ release events. Results support the possibility that pathological accumulation of MTM1 substrates may acutely depress ryanodine receptor-mediated Ca2+ release. Overexpression of a mCherry-tagged form of MTM1 in muscle fibres revealed a striated pattern consistent with the triadic area. Ca2+ release remained although unaffected by MTM1 overexpression and was also unaffected by the PtdIns-3-kinase inhibitor LY2940002, suggesting that the 3-phosphorylated PtdIns lipids active on voltage-activated Ca2+ release are inherently maintained at a low level, inefficient on Ca2+ release in normal conditions. This work was supported by grants from Centre National de la Recherche Scientifique (CNRS), Université Lyon 1, Association Française contre les Myopathies (AFM), Hubert Curien Partnership Balaton (TeT_10-1-2011-0723) and OTKA K107765. E.G.R. was a recipient of a fellowship from the Spanish Ministry of Education and Science (MEC, José Castillejo Program).
Published: 2014
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132. Sexual dimorphism starting from the blastocyst stage in response to an imbalanced maternal diet in a rabbit model

Author: Michèle Dahirel, Justine Bertrand-Michel, Olivier Morel, Tiphaine Aguirre-Lavin, Nathalie Peynot, Véronique Duranthon, Nathalie Beaujean, Pascale Chavatte-Palmer, Delphine Rousseau-Ralliard, Anne Tarrade, Marie-Christine Aubrière, Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), Université Paris Descartes - Paris 5 (UPD5), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0303 health sciences, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, [SDV]Life Sciences [q-bio], rabbit, Obstetrics and Gynecology, Biology, Sexual dimorphism, Andrology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, medicine.anatomical_structure, Reproductive Medicine, Internal medicine, sexual dimorphism, medicine, Rabbit model, Blastocyst, Stage (cooking), 030304 developmental biology, Developmental Biology
Abstract: absent
Published: 2013
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133. Phosphoinositide substrates of myotubularin affect voltage-activated Ca²⁺ release in skeletal muscle

Author: Estela González, Rodríguez, Romain, Lefebvre, Dóra, Bodnár, Claude, Legrand, Peter, Szentesi, János, Vincze, Karine, Poulard, Justine, Bertrand-Michel, Laszlo, Csernoch, Anna, Buj-Bello, and Vincent, Jacquemond
Subjects: Mice, Phosphatidylinositol Phosphates, Muscle Fibers, Skeletal, Action Potentials, Animals, Calcium, Calcium Channels, Protein Tyrosine Phosphatases, Non-Receptor, Excitation Contraction Coupling
Abstract: Skeletal muscle excitation–contraction (E–C) coupling is altered in several models of phosphatidylinositol phosphate (PtdInsP) phosphatase deficiency and ryanodine receptor activity measured in vitro was reported to be affected by certain PtdInsPs, thus prompting investigation of the physiological role of PtdInsPs in E–C coupling. We measured intracellular Ca2+ transients in voltage-clamped mouse muscle fibres microinjected with a solution containing a PtdInsP substrate (PtdIns(3,5)P2 or PtdIns(3)P) or product (PtdIns(5)P or PtdIns) of the myotubularin phosphatase MTM1. No significant change was observed in the presence of either PtdIns(5)P or PtdIns but peak SR Ca2+ release was depressed by ~30% and 50% in fibres injected with PtdIns(3,5)P2 and PtdIns(3)P, respectively, with no concurrent alteration in the membrane current signals associated with the DHPR function as well as in the voltage dependence of Ca2+ release inactivation. In permeabilized muscle fibres, the frequency of spontaneous Ca2+ release events was depressed in the presence of the three tested phosphorylated forms of PtdInsP with PtdIns(3,5)P2 being the most effective, leading to an almost complete disappearance of Ca2+ release events. Results support the possibility that pathological accumulation of MTM1 substrates may acutely depress ryanodine receptor-mediated Ca2+ release. Overexpression of a mCherry-tagged form of MTM1 in muscle fibres revealed a striated pattern consistent with the triadic area. Ca2+ release remained although unaffected by MTM1 overexpression and was also unaffected by the PtdIns-3-kinase inhibitor LY2940002, suggesting that the 3-phosphorylated PtdIns lipids active on voltage-activated Ca2+ release are inherently maintained at a low level, inefficient on Ca2+ release in normal conditions.
Published: 2013

134. Essential fatty acids deficiency promotes lipogenic gene expression and hepatic steatosis through the liver X receptor

Author: Philippe Costet, Alexandra Montagner, Alice Marmugi, Thierry Pineau, Hervé Guillou, Pascal G.P. Martin, Catherine Postic, Simon Ducheix, Justine Bertrand-Michel, Arnaud Polizzi, Silvère Baron, Frédéric Lasserre, Talal Al Saati, Laila Mselli-Lakhal, Jérôme Boué, Normand Podechard, Maud Chétiveaux, Jean-Marc A. Lobaccaro, Gilles Dietrich, Vassilia Theodorou, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), MetaToul Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Stress, membrane et signalisation (SMS), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-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 de Rennes (UR)-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 ), ANEXPLO, Institut de pharmacologie et de biologie structurale (IPBS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre de Physiopathologie Toulouse Purpan (CPTP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INRA-FORMAS France-Sweden cooperative program, Region Midi-Pyrenees, ANR, Ministere de l'Enseignement Superieur et de la Recherche, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateau MetaToul-LIPIDOMIQUE, Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul, Plateau de lipidomique, ANEXPLO / CREFRE, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-SANOFI Recherche-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aventis, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Le Corre, Morgane, ToxAlim ( ToxAlim ), Institut National Polytechnique [Toulouse] ( INP ) -Institut National de la Recherche Agronomique ( INRA ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse ( ENVT ), Institut National Polytechnique de Toulouse ( INPT ) -Institut National Polytechnique de Toulouse ( INPT ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -MetaToul, Plateau de lipidomique, Stress, membrane et signalisation ( SMS ), Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -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 des Antilles ( UA ) -Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -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 des Antilles ( UA ), Aventis-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -SANOFI Recherche-Université Toulouse III - Paul Sabatier ( UPS ), unité de recherche de l'institut du thorax UMR1087 UMR6291 ( ITX ), Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Unité de Nutrition Humaine ( UNH ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université, Centre de Physiopathologie de Toulouse Purpan ( CPTP ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Male, Steatosis, Gene Expression, Peroxisome proliferator-activated receptor, Mice, 0302 clinical medicine, Liver X Receptors, Mice, Knockout, chemistry.chemical_classification, 0303 health sciences, Fatty liver, Orphan Nuclear Receptors, Up-Regulation, 3. Good health, Cholesterol, Liver, Biochemistry, Docosahexaenoic acid, 030220 oncology & carcinogenesis, Lipogenesis, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Female, LXR, Polyunsaturated fatty acid, medicine.medical_specialty, Mice, Transgenic, Biology, 03 medical and health sciences, Internal medicine, medicine, Animals, Liver X receptor, Triglycerides, 030304 developmental biology, Fatty Acids, Essential, Hepatology, Fatty acid, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Dietary Fats, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Fatty Liver, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, chemistry, Polyunsaturated fatty acids, Deficiency Diseases, Transcription Factors
Abstract: International audience; BACKGROUND & AIMS: Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. METHODS: We used wild type mice and mice lacking Liver X Receptors to perform a nutrigenomic study that aimed at examining the role of these transcription factors. RESULTS: We showed that, in the absence of Liver X Receptors, essential fatty acids deficiency does not promote steatosis. Consistent with this, Liver X Receptors are required for the elevated expression of genes involved in lipogenesis in response to essential fatty acids deficiency. CONCLUSIONS: This work identifies, for the first time, the central role of Liver X Receptors in steatosis induced by essential fatty acids deficiency.
Published: 2013
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135. Lipidomic and Spatio-Temporal Imaging of Fat by Mass Spectrometry in Mice Duodenum during Lipid Digestion

Author: Valérie Bézirard, David Touboul, Alain Brunelle, Michela Cantiello, Véronique Roques, Justine Bertrand-Michel, Alexandre Seyer, Michel Nauze, Christine Coméra, Xavier Collet, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), ANR/PNRA (National program for diet and nutrition research) [5.34], Institut de Chimie des Substances Naturelles (CNRS), PNRA [5.34], Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de nutrition et neuro-gastroentérologie, Institut National de la Recherche Agronomique (INRA)-PRES Université de Toulouse-El-Purpan-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Pharmacologie et Toxicologie, Institut National de la Recherche Agronomique (INRA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut Claudius Regaud-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de lutte contre le cancer (CLCC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Brunet, Jocelyne
Subjects: Proteomics, Anatomy and Physiology, Digestive Physiology, lcsh:Medicine, Gene Expression, Hormone-sensitive lipase, Veterinary Anatomy and Physiology, Animal Digestive Anatomy, 030204 cardiovascular system & hematology, Biochemistry, Microsomal triglyceride transfer protein, Analytical Chemistry, Mice, 0302 clinical medicine, Lipid droplet, Molecular Cell Biology, Chylomicrons, Acetyl-CoA C-Acetyltransferase, lcsh:Science, 0303 health sciences, Multidisciplinary, Spectrometric Identification of Proteins, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Fatty Acids, Lipids, Chemistry, Cholesterol, Medicine, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, Lipid digestion, Research Article, Taurocholic Acid, medicine.medical_specialty, Duodenum, Sterol O-acyltransferase, Biology, N-Acetylglucosaminyltransferases, 03 medical and health sciences, Internal medicine, medicine, Animals, Triglycerides, 030304 developmental biology, Nutrition, Digestive Functions, lcsh:R, Lipid metabolism, Biological Transport, Lipase, Lipid Aggregates, Sterol Esterase, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Lipid Metabolism, Dietary Fats, Mice, Inbred C57BL, Endocrinology, Enterocytes, Intestinal Absorption, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Adipose triglyceride lipase, biology.protein, lcsh:Q, Veterinary Science, Carrier Proteins, Digestive System, Chylomicron, Sterol O-Acyltransferase
Abstract: International audience; Intestinal absorption of dietary fat is a complex process mediated by enterocytes leading to lipid assembly and secretion of circulating lipoproteins as chylomicrons, vLDL and intestinal HDL (iHDL). Understanding lipid digestion is of importance knowing the correlation between excessive fat absorption and atherosclerosis. By using time-of-flight secondary ion mass spectrometry (TOF-SIMS), we illustrated a spatio-temporal localization of fat in mice duodenum, at different times of digestion after a lipid gavage, for the first time. Fatty acids progressively increased in enterocytes as well as taurocholic acid, secreted by bile and engaged in the entero-hepatic re-absorption cycle. Cytosolic lipid droplets (CLD) from enterocytes were originally purified separating chylomicron-like, intermediate droplets and smaller HDL-like. A lipidomic quantification revealed their contents in triglycerides, free and esterified cholesterol, phosphatidylcholine, sphingomyelin and ceramides but also in free fatty acids, mono- and di-acylglycerols. An acyl-transferase activity was identified and the enzyme monoacylglycerol acyl transferase 2 (MGAT2) was immunodetected in all CLD. The largest droplets was also shown to contain the microsomal triglyceride transfer protein (MTTP), the acyl-coenzyme A-cholesterol acyltransferases (ACAT) 1 and 2, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). This highlights the fact that during the digestion of fats, enterocyte CLD contain some enzymes involved in the different stages of the metabolism of diet fatty acids and cholesterol, in anticipation of the crucial work of endoplasmic reticulum in the process. The data further underlines the dual role of chylomicrons and iHDL in fat digestion which should help to efficiently complement lipid-lowering therapy.
Published: 2013
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136. A systems biology approach to the hepatic role of the oxysterol receptor LXR in the regulation of lipogenesis highlights a cross-talk with PPARα

Author: Stefania Murzilli, Frédéric Lasserre, Jean-Marc A. Lobaccaro, Normand Podechard, Arnaud Polizzi, Justine Bertrand-Michel, Thierry Pineau, Chiara Di Lisio, Alexandra Montagner, Pascal G.P. Martin, Nicolas Loiseau, Hervé Guillou, Simon Ducheix, Simona D'Amore, Aurélien Pommier, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Stress, membrane, signalisation, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-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 de Rennes (UR)-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 ), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Laboratory of Lipid Metabolism and Cancer, Consorzio Mario NegriSud, MetaToul Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Physiopathologie Toulouse Purpan (CPTP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INRA-FORMAS France-Sweden cooperative program, Region Midi-Pyrenees, ANR project (Crisalis), Ministere de l'Enseignement Superieur et de la Recherche, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), Plateau MetaToul-LIPIDOMIQUE, Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul, Plateau de lipidomique, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Le Corre, Morgane, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de recherche en santé, environnement et travail (Irset), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: Male, Steatosis, Hydrocarbons, Fluorinated, MESH: Sulfonamides, Peroxisome proliferator-activated receptor, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Protein Isoforms, Ligands, Biochemistry, PPARα, Mice, 0302 clinical medicine, Cytochrome P-450 Enzyme System, Fenofibrate, MESH: Ligands, Protein Isoforms, MESH: Animals, MESH: PPAR alpha, Beta oxidation, Liver X Receptors, Oligonucleotide Array Sequence Analysis, chemistry.chemical_classification, 0303 health sciences, Sulfonamides, Systems Biology, Fatty Acids, General Medicine, Orphan Nuclear Receptors, MESH: Fatty Acids, Liver, MESH: Orphan Nuclear Receptors, 030220 oncology & carcinogenesis, MESH: Systems Biology, Lipogenesis, MESH: Cytochrome P-450 Enzyme System, lipids (amino acids, peptides, and proteins), LXR, Transcriptional Activation, medicine.medical_specialty, Oxysterol, MESH: Mice, Transgenic, MESH: Receptor Cross-Talk, Mice, Transgenic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Retinoid X receptor, 03 medical and health sciences, Internal medicine, medicine, Animals, PPAR alpha, Cytochrome P450 Family 4, Liver X receptor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, 030304 developmental biology, MESH: Lipogenesis, [SDV.GEN]Life Sciences [q-bio]/Genetics, Fatty acid, Receptor Cross-Talk, MESH: Fenofibrate, MESH: Male, MESH: Hydrocarbons, Fluorinated, Endocrinology, Nuclear receptor, chemistry, MESH: Oligonucleotide Array Sequence Analysis, MESH: Transcriptional Activation, MESH: Liver
Abstract: International audience; 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.
Published: 2013
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137. Enhanced skeletal muscle lipid oxidative efficiency in insulin-resistant vs insulin-sensitive nondiabetic, nonobese humans

Author: Aude Dupuy, Jose E. Galgani, Thierry Levade, Karla Vasquez, Cedric Moro, Guillermo Watkins, and Justine Bertrand-Michel
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Ideal Body Weight, Context (language use), Oxidative phosphorylation, Efficiency, Mitochondrion, Biochemistry, Oxidative Phosphorylation, Young Adult, Endocrinology, Insulin resistance, Downregulation and upregulation, Internal medicine, medicine, Citrate synthase, Humans, Muscle, Skeletal, biology, Insulin, Biochemistry (medical), Skeletal muscle, medicine.disease, Lipid Metabolism, Mitochondria, Muscle, Up-Regulation, medicine.anatomical_structure, biology.protein, Female, Insulin Resistance, Oxidation-Reduction
Abstract: Skeletal muscle insulin resistance is proposed to result from impaired skeletal muscle lipid oxidative capacity. However, there is no evidence indicating that muscle lipid oxidative capacity is impaired in healthy otherwise insulin-resistant individuals.The objective of the study was to assess muscle lipid oxidative capacity in young, nonobese, glucose-tolerant, insulin-resistant vs insulin-sensitive individuals.In 13 insulin-sensitive [by Matsuda index (MI) (22.6 ± 0.6 [SE] kg/m(2)); 23 ± 1 years; MI 5.9 ± 0.1] and 13 insulin-resistant (23.2 ± 0.6 kg/m(2); 23 ± 3 years; MI 2.2 ± 0.1) volunteers, skeletal muscle biopsy, blood extraction before and after an oral glucose load, and dual-energy x-ray absorptiometry were performed.Skeletal muscle mitochondrial to nuclear DNA ratio, oxidative phosphorylation protein content, and citrate synthase and β-hydroxyacyl-CoA dehydrogenase activities were assessed. Muscle lipids and palmitate oxidation ((14)CO2 and (14)C-acid soluble metabolites production) at 4 [1-(14)C]palmitate concentrations (45-520 μM) were also measured.None of the muscle mitochondrial measures showed differences between groups, except for a higher complex V protein content in insulin-resistant vs insulin-sensitive volunteers (3.5 ± 0.4 vs 2.2 ± 0.4; P = .05). Muscle ceramide content was significantly increased in insulin-resistant vs insulin-sensitive individuals (P = .04). Total palmitate oxidation showed a similar concentration-dependent response in both groups (P = .69). However, lipid oxidative efficiency (CO2 to (14)C-acid soluble metabolites ratio) was enhanced in insulin-resistant vs insulin-sensitive individuals, particularly at the highest palmitate concentration (0.24 ± 0.04 vs 0.12 ± 0.02; P = .02).We found no evidence of impaired muscle mitochondrial oxidative capacity in young, nonobese, glucose-tolerant, otherwise insulin-resistant vs insulin-sensitive individuals. Enhanced muscle lipid oxidative efficiency in insulin resistance could be a potential mechanism to prevent further lipotoxicity.
Published: 2013

138. TNFα gene knockout differentially affects lipid deposition in liver and skeletal muscle of high-fat-diet mice

Author: Christophe Giraudet, Nicolas Tardif, Carole Boue-Vaysse, Jean-Michel Chardigny, Yves Boirie, Stéphane Walrand, Jérôme Salles, Justine Bertrand-Michel, Philippe Denis, Véronique Patrac, Isabelle Mothe-Satney, Christelle Guillet, Jean-François Landrier, Lydie Combaret, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Laboratoire de Génie Civil et d'Ingénierie Environnementale (LGCIE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dysfonctions métaboliques et diabètes: Mécanismes et approches thérapeutiques, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne (UCA), Université de Provence - Aix-Marseille 1, Université de la Méditerranée - Aix-Marseille 2, Université de Nice Sophia-Antipolis (UNSA), French National Research Agency ('ANR Lip-Age'), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA)
Subjects: Liver Cirrhosis, Male, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Adipose tissue, Fatty Acids, Nonesterified, Biochemistry, DEFICIENT MICE, chemistry.chemical_compound, Mice, 0302 clinical medicine, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, Mice, Knockout, 0303 health sciences, TRIGLYCERIDE SYNTHESIS, Nutrition and Dietetics, Chemistry, INDUCED OBESITY, Organ Size, 3. Good health, medicine.anatomical_structure, High-fat diet, Lipotoxicity, Adipose Tissue, Liver, Cytokines, medicine.symptom, medicine.medical_specialty, TNF alpha-KO mice, 030209 endocrinology & metabolism, Inflammation, Ceramides, Diet, High-Fat, Gene Expression Regulation, Enzymologic, Proinflammatory cytokine, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Animals, HEPATIC STEATOSIS, Muscle, Skeletal, PROTEIN-KINASE-B, Molecular Biology, 030304 developmental biology, Fatty acid metabolism, Tumor Necrosis Factor-alpha, Skeletal muscle, Fatty acid, NECROSIS-FACTOR-ALPHA, medicine.disease, Lipid Metabolism, Fibrosis, ADIPOSE-TISSUE EXPANDABILITY, Endocrinology, ADIPOCYTE BIOLOGY, GLUCOSE-TOLERANCE, Insulin Resistance, INDUCED INSULIN-RESISTANCE
Abstract: Aims/hypothesis: Inflammation and ectopic lipid deposition contribute to obesity-related insulin resistance (IR). Studies have shown that deficiency of the proinflammatory cytokine tumor necrosis factor-alpha (INF alpha) protects against the IR induced by a high-fat diet (HFD). We aimed to evaluate the relationship between HFD-related inflammation and lipid deposition in skeletal muscle and liver. Experimental design: Wild-type (WT) and TNF alpha-deficient (TNF alpha-KO) mice were subjected to an HFD for 12 weeks. A glucose tolerance test was performed to evaluate IR. Inflammatory status was assessed by measuring plasma and tissue transcript levels of cytokines. Lipid intermediate concentrations were measured in plasma, muscle and liver. The expression of genes involved in fatty acid transport, synthesis and oxidation was analyzed in adipose tissue, muscle and liver. Results: HFD induced a higher body weight gain in TNF alpha-KO mice than in WT mice. The weight of epididymal and abdominal adipose tissues was twofold lower in WT mice than in TNF alpha-KO mice, whereas liver weight was significantly heavier in WT mice. IR, systemic and adipose tissue inflammation, and plasma nonesterified fatty acid levels were reduced in TNF alpha-KO mice fed an HFD. INFa deficiency improved fatty acid metabolism and had a protective effect against lipid deposition, inflammation and fibrosis associated with HFD in liver but had no impact on these markers in muscle. Conclusions: Our data suggest that in an HFD context, TNF alpha deficiency reduced hepatic lipid accumulation through two mechanisms: an increase in adipose tissue storage capacity and a decrease in fatty acid uptake and synthesis in the liver. (C) 2012 Elsevier Inc. All rights reserved.
Published: 2012
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139. Un régime enrichi en cholestérol et en lipides perturbe le développement fœtal et la fonction placentaire, dans un modèle lapin

Author: Anne Couturier-Tarrade, Marie-Christine Aubrière, Olivier Morel, Nicole Charpentier, Justine Bertrand-Michel, Pascale Chavatte-Palmer, Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), UMR 1048-12MC, Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Université de Genève (Unige). CHE.
Subjects: lapine, développement foetal, régime enrichi, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract: Nous avons montré qu'un régime enrichi en lipides (8%) et en cholestérol (0,2%) (régime HH) administré à des lapines à partir de l'âge de 10 semaines (avant la puberté) et pendant la gestation induisait un retard de croissance intra-utérin et augmentait la susceptibilité des descendants à développer une adiposité augmentée, un excès pondéral et une hypertension à l'âge adulte. Afin d'examiner le lien entre le développement fœtal et les conséquences métaboliques à long terme, le développement placentaire a été étudié dans ce modèle. Huit lapines adultes ont été nourries avec un régime témoin (T) ou HH à partir de l'âge de 10 semaines puis saillies à 18 semaines. A 28 jours de gestation (terme = 31 jours), les animaux ont été anesthésiés et une laparotomie a été effectuée pour analyser des flux placentaires par angiographie Doppler 3D et pour collecter le sang fœtal,les fœtus et les placentas. Bien qu'il n'y ait pas de différence significative dans le nombre de fœtus entre les deux groupes (T :7,6 ±0,95 fœtus; HH : 8,2 ±0,5 fœtus/portée), le poids des fœtus était significativement réduit dans le groupe HH par rapport aux témoins (29,08±0,88 vs 35,37±1,17 g; p
Published: 2012

140. Spatial distribution of brain ceramides in an acid ceramidase deficient murine model: Subsequent histological manifestations and functional deficits

Author: Josefina Casas, Christopher K. Dunn, Aude Dupuy, Pauline Le Faouder, Shaalee Dworski, Ingrid Xuan, Tomo Sawada, Thierry Levade, David R. Hampson, Jeffrey A. Medin, Gemma Fabriàs, Richard R. Drake, Matthew C. Micsenyi, Elizabeth E. Jones, Stéphane Carpentier, Justine Bertrand-Michel, Steven U. Walkley, Jakub Sikora, and Mustafa Kamani
Subjects: education.field_of_study, Mutation, Pathology, medicine.medical_specialty, medicine.diagnostic_test, Endocrinology, Diabetes and Metabolism, Population, Globotriaosylceramide, Biology, medicine.disease, medicine.disease_cause, Biochemistry, Fabry disease, chemistry.chemical_compound, Endocrinology, Germline mutation, chemistry, Immunology, Biopsy, Genetics, medicine, education, Molecular Biology, Index case, X-linked recessive inheritance
Abstract: Background: Fabry disease (FD) is an innate error of glycosphingolipid catabolism due to a genetic defect in the gene which codifies for alphagalactosidase A (α-Gal A) production (GLA gene). Mutations affecting the GLA gene result in deficiency of this lysosomal enzyme, which in turn leads to progressive accumulation of neutral glycosphingolipids, primarily globotriaosylceramide (GL-3), in different cell types throughout the body, including renal glomerular and tubular epithelial cells, myocardial cells and valvular fibrocytes, and nervous system. FD has an X linked inheritance. Currently, more than 600 disease-causing mutations in the GLA gene have been described. Most of these mutations are private, restricted to an individual family. De novo mutations are rare; population reports establish their frequency between 4 and 7%. We present the case of a pediatric male patient with a previously unreported de novomutation, which during family tree analysis, revealed a positive sibling, but nomutation found in the mother. Case presentation: A 17 year old male patient from Durango, Mexico with a negative family history presented at our ward. His initial symptoms began at 10 years of age and were primarily neurological: recurrent and progressive acroparesthesias several times a week, upper and lower extremity weaknesswithmovement limitations and fainting spells; he also complained of intermittent fever, hypohidrosis, abdominal pain and diarrhea. Clinical evaluation of the patient revealed tortuosity of retinal vessels, sinus bradycardia and hypotension and distal hyperesthesia in arms and legs. Fabry disease was suspected; αGal A enzyme activity, GLA gene analysis and lysoGL-3 measurement confirmed the diagnosis. Family tree evaluation was carried out; one six-year-old brother also had the mutation; however no mutation was found in the mother’s molecular analysis. FD specific evaluation of the index case revealed positive 24-hour proteinuria (6.5 mg/kg/h reference b4 ml/kg/h); CNSMRI was normal. Kidney biopsy was conducted; electron microscopy analysis of specimens revealed dense lamellar bodies corresponding to lipid material deposits in all cell groups, confirming the presence of a pathological mutation. Conclusions: De novo onset mutations in FD are rare; however, even more infrequent is the presence of germline mutations, which have been reported only periodically in case reports. Unfortunately, female germline cells are difficult to obtain to confirm this diagnosis. doi:10.1016/j.ymgme.2014.12.069
Published: 2015
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141. Role of low-density lipoprotein receptor in the hepatitis C virus life cycle

Author: Anne Op De Beeck, Lucie Goueslain, Gilles Duverlie, Sandrine Belouzard, Justine Bertrand-Michel, François Tercé, Yves Rouille, Jean Dubuisson, Anna Albecka, and Véronique Descamps
Subjects: Small interfering RNA, Hepatitis C virus, media_common.quotation_subject, CHO Cells, Hepacivirus, Biology, medicine.disease_cause, Kidney, Virus Replication, Antibodies, Cricetulus, Viral entry, Cell Line, Tumor, Cricetinae, medicine, Animals, Humans, Internalization, media_common, Lipoprotein lipase, Life Cycle Stages, Hepatology, Ovary, nutritional and metabolic diseases, virus diseases, RNA, Virology, digestive system diseases, HEK293 Cells, Receptors, LDL, LDL receptor, Hepatocytes, RNA, Viral, lipids (amino acids, peptides, and proteins), Female, Lipoprotein
Abstract: Hepatitis C virus (HCV) particles are known to be in complex with lipoproteins. As a result of this interaction, the low-density lipoprotein (LDL) receptor (LDLR) has been proposed as a potential entry factor for HCV; however, its implication in virus entry remains unclear. Here, we reinvestigated the role of the LDLR in the HCV life cycle by comparing virus entry to the mechanism of lipoprotein uptake. A small interfering RNA targeting the LDLR in Huh-7 cells reduced HCV infectivity, confirming that this receptor plays a role in the life cycle of HCV generated in cell culture. However, kinetics of internalization were much faster for lipoproteins than for infectious HCV particles. Furthermore, a decrease in HCV RNA replication was observed by blocking the LDLR with a specific antibody, and this was associated with an increase in the ratio of phosphatidylethanolamine to phosphatidylcholine in host cells. Nevertheless, a soluble form of the LDLR inhibited both HCV entry into the hepatocytes and its binding to the LDLR expressed on Chinese hamster ovary cells, suggesting a direct interaction between the HCV particle and the LDLR. Finally, we showed that modification of HCV particles by lipoprotein lipase (LPL) reduces HCV infectivity and increases HCV binding to LDLR. Importantly, LPL treatment also induced an increase in RNA internalization, suggesting that LDLR, at least in some conditions, leads to nonproductive internalization of HCV. Conclusion: The LDLR is not essential for infectious HCV particle entry, whereas the physiological function of this receptor is important for optimal replication of the HCV genome. (HEPATOLOGY 2012)
Published: 2011

142. Oleate-enriched diet improves insulin sensitivity and restores muscle protein synthesis in old rats

Author: Jean-Michel Chardigny, Lydie Combaret, Jérôme Salles, Justine Bertrand-Michel, Yves Boirie, Christophe Giraudet, Véronique Patrac, Carole Boue-Vaysse, Isabelle Mothe-Satney, Christelle Guillet, Jean-François Landrier, Carole Migné, N. Tardif, Stéphane Walrand, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Nutriments Lipidiques et Prévention des Maladies Métaboliques, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nice Sophia-Antipolis (UNSA), Institut des corps gras (ITERG), Institut Fédératif de Recherche 150 - Bio-Médicale de Toulouse, This study was funded by the French National Research Agency ('ANR Lip-Age')., Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Digestif, Centre Hospitalier Universitaire de Nice (CHU Nice), Equipe Nutrition, Santé et Biochimie des Lipides (ITERG), Inst Federatif Rech Biomed, Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université de la Méditerranée - Aix-Marseille 2, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nice (CHU de Nice), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Anabolism, protein synthesis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Interleukin-1beta, Peroxisome Proliferator-Activated Receptors, Adipose tissue, Muscle Proteins, Critical Care and Intensive Care Medicine, Acyl-CoA Dehydrogenase, Random Allocation, 0302 clinical medicine, Myocyte, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, 0303 health sciences, nutrition and dietetics, Reverse Transcriptase Polymerase Chain Reaction, Age Factors, Postprandial, medicine.anatomical_structure, high-fat diet, nutrition, Adipose Tissue, medicine.symptom, medicine.medical_specialty, 030209 endocrinology & metabolism, Inflammation, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Animals, RNA, Messenger, skeletal muscle, Rats, Wistar, Muscle, Skeletal, 030304 developmental biology, Carnitine O-Palmitoyltransferase, business.industry, Tumor Necrosis Factor-alpha, Insulin, aging, Skeletal muscle, medicine.disease, Rats, Endocrinology, Insulin Resistance, business, Oleic Acid
Abstract: International audience; Background & aims: Age-related inflammation and insulin resistance (IR) have been implicated in the inability of old muscles to properly respond to anabolic stimuli such as amino acids (AA) or insulin. Since fatty acids can modulate inflammation and IR in muscle cells, we investigated the effect of palmitate-enriched diet and oleate-enriched diet on inflammation, IR and muscle protein synthesis (MPS) rate in old rats.Methods: Twenty-four 25-month-old rats were fed either a control diet (OC), an oleate-enriched diet (HFO) or a palmitate-enriched diet (HFP) for 16 weeks. MPS using labeled amino acids and mTOR activation were assessed after AA and insulin anabolic stimulation to mimic postprandial state.Results: IR and systemic and adipose tissue inflammation (TNF alpha. and IL1 beta) were improved in the HFO group. Muscle genes controlling mitochondrial beta-oxidation (PPARs, MCAD and CPT-1b) were up-regulated in the HFO group. AA and insulin-stimulated MPS in the HFO group only, and this stimulation was related to activation of the Akt/mTOR pathway.Conclusions: The age-related MPS response to anabolic signals was improved in rats fed an oleate-enriched diet. This effect was related to activation of muscle oxidative pathways, lower IR, and a decrease in inflammation.
Published: 2011
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143. Is Crohn’s creeping fat an adipose tissue?

Author: Jean-Pierre Segain, Laurent Ferrier, Isabelle Olivier, Philippe Valet, Valérie Bézirard, Sylvain Kirzin, Robert Ducroc, Helene Eutamene, J Moreau, Christel Cartier, Justine Bertrand-Michel, Isabelle Castan-Laurell, Jean-Pierre Duffas, Hervé Guillou, Vassilia Theodorou, Guillaume Portier, Eutamene, Hélène, Unité de nutrition et neuro-gastroentérologie, Institut National de la Recherche Agronomique (INRA)-PRES Université de Toulouse-El-Purpan-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacologie et Toxicologie, Institut National de la Recherche Agronomique (INRA), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Chirurgie Générale et Digestive [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Chirurgie Générale et Digestive [Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, Physiologie des Adaptations Nutritionnelles (PhAN), Neuro-Gastroentérologie et Nutrition (NGN), Institut National de la Recherche Agronomique (INRA)-Ecole supérieure d'agriculture de Purpan (ESAP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Simon, Marie Francoise
Subjects: Male, Pathology, [SDV]Life Sciences [q-bio], Adipose tissue, Cystic fibrosis, Immunoenzyme Techniques, Mice, 0302 clinical medicine, Crohn Disease, MESH: Peroxidase, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Colitis, Immunology and Allergy, Medicine, MESH: Animals, Mesentery, 0303 health sciences, Crohn's disease, Mice, Inbred BALB C, Reverse Transcriptase Polymerase Chain Reaction, Gastroenterology, MESH: Enzyme-Linked Immunosorbent Assay, Colitis, Lipids, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Adipose Tissue, 030211 gastroenterology & hepatology, medicine.symptom, MESH: Adipose Tissue, MESH: Dinitrofluorobenzene, medicine.medical_specialty, Blotting, Western, MESH: Mice, Inbred BALB C, creeping fat, mesenteric adipose tissue, Crohn’s disease, animal model, Inflammation, Enzyme-Linked Immunosorbent Assay, 03 medical and health sciences, Animal model, MESH: Blotting, Western, Animals, Humans, RNA, Messenger, MESH: Immunoenzyme Techniques, MESH: Mesentery, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, Peroxidase, MESH: Humans, MESH: Crohn Disease, business.industry, Body Weight, medicine.disease, MESH: Lipids, MESH: Male, MESH: Body Weight, Mesenteric adipose tissue, Dinitrofluorobenzene, business, Human Pathology
Abstract: International audience; BACKGROUND: In human pathology, the "creeping fat" (CF) of the mesentery is unique to Crohn's disease (CD). CF is usually referred to as an ectopic extension of mesenteric adipose tissue (MAT). However, since no animal model developing CF has ever been established, very little is known about this type of fat-depot expansion and its role in the development of the disease. METHODS: We developed and standardized an experimental protocol in mice that reproducibly induces CF development when a severe colonic inflammation is obtained by intracolonic instillation of DNBS. RESULTS: Macro-microscopic observations revealed a fatty appearance of CF. Yet when compared to MAT from the same animals, CF contains very little triglycerides, few adipocytes, and we observed a very low expression and protein levels of both adipose markers (hormone-sensitive lipase, perilipin) and adipocytokines (leptin, adiponectin). The decreased expression of perilipin in CF was also observed by immunohistochemistry. Conversely, the expression of proinflammatory and fibrous markers (Pref-1) was much higher in CF than in MAT. These observations were fully consistent with those made on CF recovered from five CD patients and compared with subcutaneous and mesenteric fat from the same patients. CONCLUSIONS: Altogether, this work reports an original experimental mice model of CF. In this model we establish for the first time that CF only occurs in severe colonic inflammation and shows an inflammatory, fibrous but not an adipose pattern.
Published: 2011
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144. 13-HODE is the major PPARγ ligand secreted by human cytotrophoblasts upon infection by HCMV

Author: Thierry Fournier, Justine Bertrand-Michel, Stéphane Chavanas, Kaoutar Leghmari, Christian Davrinche, Hélène Martin, Nicolas Cenac, Benjamin Rauwel, and Pauline Le Faouder
Subjects: Reproductive Medicine, Chemistry, Pparγ ligand, Cancer research, Obstetrics and Gynecology, Cytotrophoblasts, Virology, Developmental Biology
Published: 2014
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145. Rituximab inhibits B-cell receptor signaling

Author: Guy Laurent, S Kheirallah, Jean-Jacques Fournié, Anne Quillet-Mary, Christine Bezombes, Pierre Caron, Emilie Gross, Justine Bertrand-Michel, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'hématologie [Hôpital Purpan, Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Claudius Regaud-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Plateforme MetaToul, and MetaboHUB
Subjects: MAPK/ERK pathway, Time Factors, [SDV]Life Sciences [q-bio], Cell, Syk, Biochemistry, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, hemic and lymphatic diseases, Receptor, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Protein Tyrosine Phosphatase, Non-Receptor Type 6, breakpoint cluster region, Intracellular Signaling Peptides and Proteins, Antibodies, Monoclonal, Hematology, Protein-Tyrosine Kinases, Flow Cytometry, 3. Good health, medicine.anatomical_structure, Cholesterol, src-Family Kinases, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, RNA Interference, Signal transduction, Rituximab, Signal Transduction, Immunology, Blotting, Western, Receptors, Antigen, B-Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, Membrane Microdomains, LYN, Cell Line, Tumor, medicine, Humans, Syk Kinase, Protein kinase B, 030304 developmental biology, Phospholipase C gamma, Cell Biology, Cancer research, Calcium, Proto-Oncogene Proteins c-akt
Abstract: Rituximab (RTX), a monoclonal antibody directed against the CD20 protein, is a drug commonly used in the treatment of B-cell–derived lymphoid neoplasias and of antibody-mediated autoimmune diseases. In addition to cell- and complement-mediated B-cell depletion, RTX is thought to inhibit B-cell survival and proliferation through negative regulation of canonical signaling pathways involving Akt, ERK, and mammalian target of rapamycin. However, surprisingly, although B-cell receptor (BCR) signaling has been considered critical for normal and more recently, for neoplastic B cells, the hypothesis that RTX could target BCR has never been investigated. Using follicular lymphoma cell lines as models, as well as normal B cells, we show here, for the first time, that pretreatment with RTX results in a time-dependent inhibition of the BCR-signaling cascade involving Lyn, Syk, PLCγ2, Akt, and ERK, and calcium mobilization. The inhibitory effect of RTX correlates with decrease of raft-associated cholesterol, complete inhibition of BCR relocalization into lipid raft microdomains, and down-regulation of BCR immunoglobulin expression. Thus, RTX-mediated alteration of BCR expression, dynamics, and signaling might contribute to the immunosuppressive activity of the drug.
Published: 2010
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146. The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans

Author: Hervé Guillou, Pierre-Damien Denechaud, Lawrence Serfaty, Fadila Benhamed, Catherine Postic, Maud Lemoine, Justine Bertrand-Michel, Jacqueline Capeau, Jean Girard, Céline Robichon, Marthe Moldes, Chantal Housset, Vlad Ratziu, Bertrand-Michel, Justine, Ratziu, Vlad, Guillou, Hervé, Postic, Catherine, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Mechanical and Materials Engineering (CeSMEC), Florida International University [Miami] (FIU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Département de Physiologie, Université de Montréal (UdeM), Department of Medicine, Imperial College London, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Fatty Acids, Monounsaturated, Mice, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, PPAR-ALPHA, Nonalcoholic fatty liver disease, Phosphorylation, ComputingMilieux_MISCELLANEOUS, GENE-EXPRESSION, XYLULOSE 5-PHOSPHATE, Metabolic Syndrome, 0303 health sciences, biology, UNFOLDED PROTEIN RESPONSE, NONALCOHOLIC STEATOHEPATITIS, MODULATES GLUCONEOGENESIS, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Fatty liver, Nuclear Proteins, General Medicine, FATTY LIVER-DISEASE, STEAROYL-COA DESATURASE, LIPID-METABOLISM, OBESE MICE, Liver, 030220 oncology & carcinogenesis, Lipogenesis, Female, Stearoyl-CoA Desaturase, medicine.medical_specialty, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Animals, Humans, 030304 developmental biology, Insulin, medicine.disease, Fatty Liver, Insulin receptor, Endocrinology, biology.protein, Steatosis, Metabolic syndrome, Insulin Resistance, Proto-Oncogene Proteins c-akt, Transcription Factors
Abstract: Nonalcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Although deposition of excess triglycerides within liver cells, a hallmark of NAFLD, is associated with a loss of insulin sensitivity, it is not clear which cellular abnormality arises first. We have explored this in mice overexpressing carbohydrate responsive element-binding protein (ChREBP). On a standard diet, mice overexpressing ChREBP remained insulin sensitive, despite increased expression of genes involved in lipogenesis/fatty acid esterification and resultant hepatic steatosis (simple fatty liver). Lipidomic analysis revealed that the steatosis was associated with increased accumulation of monounsaturated fatty acids (MUFAs). In primary cultures of mouse hepatocytes, ChREBP overexpression induced expression of stearoyl-CoA desaturase 1 (Scd1), the enzyme responsible for the conversion of saturated fatty acids (SFAs) into MUFAs. SFA impairment of insulin-responsive Akt phosphorylation was therefore rescued by the elevation of Scd1 levels upon ChREBP overexpression, whereas pharmacological or shRNA-mediated reduction of Scd1 activity decreased the beneficial effect of ChREBP on Akt phosphorylation. Importantly, ChREBP-overexpressing mice fed a high-fat diet showed normal insulin levels and improved insulin signaling and glucose tolerance compared with controls, despite having greater hepatic steatosis. Finally, ChREBP expression in liver biopsies from patients with nonalcoholic steatohepatitis was increased when steatosis was greater than 50% and decreased in the presence of severe insulin resistance. Together, these results demonstrate that increased ChREBP can dissociate hepatic steatosis from insulin resistance, with beneficial effects on both glucose and lipid metabolism.
Published: 2009
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147. Ligands of the antiestrogen-binding site induce active cell death and autophagy in human breast cancer cells through the modulation of cholesterol metabolism

Author: P. De Medina, Marc Poirot, N Boubekeur, François Tercé, Bruno Payré, Justine Bertrand-Michel, Sandrine Silvente-Poirot, Département de chimie, Affichem, Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Poirot, Marc, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul
Subjects: Pyrrolidines, Cellular differentiation, Apoptosis, Ligands, 0302 clinical medicine, MESH: Vitamin E, MESH: Cholesterol, Estrogen Receptor Modulators, Annexin, Tumor Cells, Cultured, MESH: Ligands, Vitamin E, skin and connective tissue diseases, 0303 health sciences, MESH: Reactive Oxygen Species, Cell Differentiation, MESH: Antineoplastic Agents, Hormonal, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Estrogen Receptor Modulators, 3. Good health, Cell biology, Mitochondria, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Cholesterol, 030220 oncology & carcinogenesis, Female, MESH: Cell Differentiation, Programmed cell death, Antineoplastic Agents, Hormonal, MESH: Mitochondria, Breast Neoplasms, Biology, MESH: Ethylamines, 03 medical and health sciences, Autophagy, Ethylamines, Humans, MESH: Autophagy, MESH: Tumor Cells, Cultured, Binding site, Molecular Biology, 030304 developmental biology, Binding Sites, MESH: Humans, MESH: Pyrrolidines, MESH: Apoptosis, Cell Biology, Antiestrogen, Tamoxifen, MESH: Binding Sites, Cancer cell, MESH: Tamoxifen, Reactive Oxygen Species, MESH: Female, MESH: Breast Neoplasms
Abstract: International audience; We have recently reported that cytostatic concentrations of the microsomal antiestrogen-binding site (AEBS) ligands, such as PBPE (N-pyrrolidino-(phenylmethyphenoxy)-ethanamine,HCl) and tamoxifen, induced differentiation characteristics in breast cancer cells through the accumulation of post-lanosterol intermediates of cholesterol biosynthesis. We show here that exposure of MCF-7 (human breast adenocarcinoma cell line) cells to higher concentrations of AEBS ligands triggered active cell death and macroautophagy. Apoptosis was characterized by Annexin V binding, chromatin condensation, DNA laddering and disruption of the mitochondrial functions. We determined that cell death was sterol- and reactive oxygen species-dependent and was prevented by the antioxidant vitamin E. Macroautophagy was characterized by the accumulation of autophagic vacuoles, an increase in the expression of Beclin-1 and the stimulation of autophagic flux. We established that macroautophagy was sterol- and Beclin-1-dependent and was associated with cell survival rather than with cytotoxicity, as blockage of macroautophagy sensitized cells to AEBS ligands. These results show that the accumulation of sterols by AEBS ligands in MCF-7 cells induces apoptosis and macroautophagy. Collectively, these data support a therapeutic potential for selective AEBS ligands in breast cancer management and shows a mechanism that explains the induction of autophagy in MCF-7 cells by tamoxifen and other selective estrogen receptor modulators.
Published: 2009
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148. Glutathione transferases kappa 1 and kappa 2 localize in peroxisomes and mitochondria, respectively, and are involved in lipid metabolism and respiration in Caenorhabditis elegans

Author: Elise, Petit, Xavier, Michelet, Claudine, Rauch, Justine, Bertrand-Michel, François, Tercé, Renaud, Legouis, and Fabrice, Morel
Subjects: Oxygen Consumption, Peroxisomes, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Lipid Metabolism, Glutathione Transferase, Mitochondria
Abstract: To elucidate the function of kappa class glutathione transferases (GSTs) in multicellular organisms, their expression and silencing were investigated in Caenorhabditis elegans. In contrast with most vertebrates, which possess only one GST kappa gene, two distinct genes encoding GSTK-1 and GSTK-2 are present in the C. elegans genome. The amino acid sequences of GSTK-1 and GSTK-2 share around 30% similarity with the human hGSTK1 sequence and, like the human transferase, GSTK-1 contains a C-terminal peroxisomal targeting sequence. gstk-1 and gstk-2 genes show distinct developmental and tissue expression patterns. We show that GSTK-2 is localized in the mitochondria and expressed mainly in the pharynx, muscles and epidermis, whereas GSTK-1 is restricted to peroxisomes and expressed in the intestine, body wall muscles and epidermis. In order to determine the potential role(s) of GST kappa genes in C. elegans, specific silencing of the gstk-1 and gstk-2 genes was performed by an RNA interference approach. Knockdown of gstk-1 or gstk-2 had no apparent effect on C. elegans reproduction, development, locomotion or lifespan. By contrast, when biological functions (oxygen consumption and lipid metabolism) related to peroxisomes and/or mitochondria were investigated, we observed a significant decrease in respiration rate and a lower concentration of the monounsaturated fatty acid cis-vaccenic acid (18:1omega7) when worms were fed on bacteria expressing RNA interference targeting both gstk-1 and gstk-2. These results demonstrate that GST kappa, although not essential for the worm's life, may be involved in energetic and lipid metabolism, two functions related to mitochondria and peroxisomes.
Published: 2009

149. Neurological and physiological disorders in Artemia harboring manipulative cestodes

Author: Frédéric Thomas, David Biron, Marta I. Sánchez, Dorothée Missé, Justine Bertrand-Michel, Marie-Jeanne Perrot-Minnot, Génétique et évolution des maladies infectieuses (GEMI), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD [France-Sud]), Biogéosciences [UMR 6282] [Dijon] (BGS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), HPMCT Proteome Analysis, Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Supported by a postdoctoral grant from the Ministerio de Ciencia y Tecnologia (Spain)., Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Génétique et évolution des maladies infectieuses ( GEMI ), Centre National de la Recherche Scientifique ( CNRS ), Biogéosciences [Dijon] ( BGS ), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Plateau de lipidomique, and Hôpital Purpan [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Claude de Preval
Subjects: 0106 biological sciences, Proteome, MESH : Host-Parasite Interactions, 01 natural sciences, MESH: Down-Regulation, MESH : Down-Regulation, MESH : Artemia, [ SDV.EE.IEO ] Life Sciences [q-bio]/Ecology, environment/Symbiosis, Parasite hosting, MESH: Animals, 0303 health sciences, biology, Ecology, MESH : Peptides, MESH: Peptides, MESH: Artemia, Lipids, MESH : Triglycerides, MESH: Cestoda, MESH: Proteome, MESH: Triglycerides, [ SDV.MP.PAR ] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Cestoda, Branchiopoda, Down-Regulation, Brine shrimp, MESH : Proteome, 010603 evolutionary biology, MESH: Host-Parasite Interactions, Microbiology, Host-Parasite Interactions, 03 medical and health sciences, Helminths, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Ecology, Evolution, Behavior and Systematics, Triglycerides, 030304 developmental biology, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, Host (biology), MESH : Cestoda, MESH : Lipids, biology.organism_classification, Crustacean, MESH: Lipids, MESH : Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, MESH: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Parasitology, MESH : Animals, Artemia, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Peptides, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: 5 pages; International audience; There are many impressive examples of host manipulation by parasites, but mechanisms underlying these ethological changes, as well as their physiological consequences, are not well characterized. Here, we analyzed part of the cerebral proteome of brine shrimp Artemia infected by manipulative cestodes, using for the first time the ProteinChip Surface-Enhanced Laser Desorption Ionization and Time of Fly Mass Spectrometry (SELDI-TOF MS) system, which has been proposed as an excellent way to analyze the host genome during the host-parasite interaction processes. We found 2 peptides downregulated in individuals infected by the dilepidid, Anomotaenia tringae (4.5 kDa), and by the 2 hymenolepidids, Flamingolepis liguloides and Confluaria podicipina (3.9 kDa), which are potential candidates for involvement with the manipulation process. The identification of 2 head peptides (4.1 and 4.2 kDa) overexpressed in all the categories in brine shrimp living at the surface (both infected individuals and uninfected controls) suggests its association with the different environmental conditions experienced at the water surface. In parallel, brine shrimp infected by C. podicipina showed significant values of triglycerides, potentially augmenting their profitability and attractiveness for the predaceous definitive host (grebes). We discuss our findings in relationship with current ideas on the complexity of parasitically modified organisms.
Published: 2009
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150. Microsomal antiestrogen-binding site ligands induce growth control and differentiation of human breast cancer cells through the modulation of cholesterol metabolism

Author: Isabelle Fourquaux, Philippe de Medina, Nadia Boubekeur, Bruno Payré, Sandrine Silvente-Poirot, Loubna Mhamdi, Marc Poirot, François Tercé, Justine Bertrand-Michel, Dominique Goudounèche, Michel Record, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Département de chimie, Affichem, Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Poirot, Marc, Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: Cancer Research, Time Factors, Cellular differentiation, MESH: Flow Cytometry, Ligands, 0302 clinical medicine, MESH: Cholesterol, Estrogen Receptor Modulators, MESH: Ligands, 0303 health sciences, Cell Differentiation, Cell cycle, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Flow Cytometry, Milk Proteins, Lipids, MESH: Estrogen Receptor Modulators, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Cholesterol, Oncology, Biochemistry, 030220 oncology & carcinogenesis, Intracellular, MESH: Cell Differentiation, MESH: Milk Proteins, MESH: Cell Line, Tumor, Breast Neoplasms, Biology, MESH: Microsomes, 03 medical and health sciences, Cell Line, Tumor, Microsomes, MESH: Cell Proliferation, Humans, Binding site, 030304 developmental biology, Cell Proliferation, Binding Sites, MESH: Humans, Cell growth, MESH: Time Factors, Antiestrogen, MESH: Lipids, Tamoxifen, MESH: Binding Sites, Cell culture, Cancer cell, Cancer research, MESH: Tamoxifen, MESH: Breast Neoplasms
Abstract: The microsomal antiestrogen-binding site (AEBS) is a high-affinity membranous binding site for the antitumor drug tamoxifen that selectively binds diphenylmethane derivatives of tamoxifen such as PBPE and mediates their antiproliferative properties. The AEBS is a hetero-oligomeric complex consisting of 3β-hydroxysterol-Δ8-Δ7-isomerase and 3β-hydroxysterol-Δ7-reductase. High-affinity AEBS ligands inhibit these enzymes leading to the massive intracellular accumulation of zymostenol or 7-dehydrocholesterol (DHC), thus linking AEBS binding to the modulation of cholesterol metabolism and growth control. The aim of the present study was to gain more insight into the control of breast cancer cell growth by AEBS ligands. We report that PBPE and tamoxifen treatment induced differentiation in human breast adenocarcinoma cells MCF-7 as indicated by the arrest of cells in the G0-G1 phase of the cell cycle, the increase in the cell volume, the accumulation and secretion of lipids, and a milk fat globule protein found in milk. These effects were observed with other AEBS ligands and with zymostenol and DHC. Vitamin E abrogates the induction of differentiation and reverses the control of cell growth produced by AEBS ligands, zymostenol, and DHC, showing the importance of the oxidative processes in this effect. AEBS ligands induced differentiation in estrogen receptor-negative mammary tumor cell lines SKBr-3 and MDA-MB-468 but with a lower efficiency than observed with MCF-7. Together, these data show that AEBS ligands exert an antiproliferative effect on mammary cancer cells by inducing cell differentiation and growth arrest and highlight the importance of cholesterol metabolism in these effects. [Mol Cancer Ther 2008;7(12):3707–18]
Published: 2008
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