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2. Pharmacological activation of constitutive androstane receptor induces female-specific modulation of hepatic metabolism

Author

Huillet, Marine, Lasserre, Frédéric, Gratacap, Marie-Pierre, Engelmann, Beatrice, Bruse, Justine, Polizzi, Arnaud, Fougeray, Tiffany, Martin, Céline Marie Pauline, Rives, Clémence, Fougerat, Anne, Naylies, Claire, Lippi, Yannick, Garcia, Géraldine, Rousseau-Bacquie, Elodie, Canlet, Cécile, Debrauwer, Laurent, Rolle-Kampczyk, Ulrike, von Bergen, Martin, Payrastre, Bernard, Boutet-Robinet, Elisa, Gamet-Payrastre, Laurence, Guillou, Hervé, Loiseau, Nicolas, and Ellero-Simatos, Sandrine

Published
2024
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3. Obesity promotes fumonisin B1 hepatotoxicity

Author

Dopavogui, Léonie, Régnier, Marion, Polizzi, Arnaud, Ponchon, Quentin, Smati, Sarra, Klement, Wendy, Lasserre, Frédéric, Lukowicz, Céline, Lippi, Yannick, Fougerat, Anne, Bertrand-Michel, Justine, Naylies, Claire, Canlet, Cécile, Debrauwer, Laurent, Rousseau-Bacquié, Elodie, Gamet-Payrastre, Laurence, Dauriat, Charlène, Casas, Josefina, Croubels, Siska, De Baere, Siegrid, Burger, Hester M., Chassaing, Benoit, Ellero-Simatos, Sandrine, Guillou, Hervé, Oswald, Isabelle P., and Loiseau, Nicolas

Published
2023
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7. The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice

Author

Barretto, Sharon Ann, Lasserre, Frederic, Huillet, Marine, Régnier, Marion, Polizzi, Arnaud, Lippi, Yannick, Fougerat, Anne, Person, Elodie, Bruel, Sandrine, Bétoulières, Colette, Naylies, Claire, Lukowicz, Céline, Smati, Sarra, Guzylack, Laurence, Olier, Maïwenn, Théodorou, Vassilia, Mselli-Lakhal, Laila, Zalko, Daniel, Wahli, Walter, Loiseau, Nicolas, Gamet-Payrastre, Laurence, Guillou, Hervé, and Ellero-Simatos, Sandrine

Published
2021
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9. The protective role of liver X receptor (LXR) during fumonisin B1-induced hepatotoxicity

Author

Régnier, Marion, Polizzi, Arnaud, Lukowicz, Céline, Smati, Sarra, Lasserre, Frédéric, Lippi, Yannick, Naylies, Claire, Laffitte, Joelle, Bétoulières, Colette, Montagner, Alexandra, Ducheix, Simon, Gourbeyre, Pascal, Ellero-Simatos, Sandrine, Menard, Sandrine, Bertrand-Michel, Justine, Al Saati, Talal, Lobaccaro, Jean-Marc, Burger, Hester M., Gelderblom, Wentzel C., Guillou, Hervé, Oswald, Isabelle P., and Loiseau, Nicolas

Published
2019
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10. Author Correction: Dimorphic metabolic and endocrine disorders in mice lacking the constitutive androstane receptor

Author

Lukowicz, Céline, Ellero-Simatos, Sandrine, Régnier, Marion, Oliviero, Fabiana, Lasserre, Frédéric, Polizzi, Arnaud, Montagner, Alexandra, Smati, Sarra, Boudou, Frédéric, Lenfant, Françoise, Guzylack-Pirou, Laurence, Menard, Sandrine, Barretto, Sharon, Fougerat, Anne, Lippi, Yannick, Naylies, Claire, Bertrand-Michel, Justine, Belgnaoui, Afifa Ait, Theodorou, Vassilia, Marchi, Nicola, Gourdy, Pierre, Gamet-Payrastre, Laurence, Loiseau, Nicolas, Guillou, Hervé, and Mselli-Lakhal, Laïla

Published
2020
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11. Dimorphic metabolic and endocrine disorders in mice lacking the constitutive androstane receptor

Author

Lukowicz, Céline, Ellero-Simatos, Sandrine, Régnier, Marion, Oliviero, Fabiana, Lasserre, Frédéric, Polizzi, Arnaud, Montagner, Alexandra, Smati, Sarra, Boudou, Frédéric, Lenfant, Françoise, Guzylack-Pirou, Laurence, Menard, Sandrine, Barretto, Sharon, Fougerat, Anne, Lippi, Yannick, Naylies, Claire, Bertrand-Michel, Justine, Belgnaoui, Afifa Ait, Theodorou, Vassilia, Marchi, Nicola, Gourdy, Pierre, Gamet-Payrastre, Laurence, Loiseau, Nicolas, Guillou, Hervé, and Mselli-Lakhal, Laïla

Published
2019
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12. Haem iron reshapes colonic luminal environment: impact on mucosal homeostasis and microbiome through aldehyde formation

Author

Martin, Océane C. B., Olier, Maïwenn, Ellero-Simatos, Sandrine, Naud, Nathalie, Dupuy, Jacques, Huc, Laurence, Taché, Sylviane, Graillot, Vanessa, Levêque, Mathilde, Bézirard, Valérie, Héliès-Toussaint, Cécile, Estrada, Florence Blas Y., Tondereau, Valérie, Lippi, Yannick, Naylies, Claire, Peyriga, Lindsey, Canlet, Cécile, Davila, Anne Marie, Blachier, François, Ferrier, Laurent, Boutet-Robinet, Elisa, Guéraud, Françoise, Théodorou, Vassilia, and Pierre, Fabrice H. F.

Published
2019
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13. Dietary Amino Acid Source Elicits Sex‐Specific Metabolic Response to Diet‐Induced NAFLD in Mice.

Author

Rives, Clémence, Martin, Céline Marie Pauline, Evariste, Lauris, Polizzi, Arnaud, Huillet, Marine, Lasserre, Frédéric, Alquier‐Bacquie, Valérie, Perrier, Prunelle, Gomez, Jelskey, Lippi, Yannick, Naylies, Claire, Levade, Thierry, Sabourdy, Frédérique, Remignon, Hervé, Fafournoux, Pierre, Chassaing, Benoit, Loiseau, Nicolas, Guillou, Hervé, Ellero‐Simatos, Sandrine, and Gamet‐Payrastre, Laurence

Published
2024
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14. CAR Protects Females from Diet-Induced Steatosis and Associated Metabolic Disorders.

Author

Oliviero, Fabiana, Klement, Wendy, Mary, Lucile, Dauwe, Yannick, Lippi, Yannick, Naylies, Claire, Gayrard, Véronique, Marchi, Nicola, and Mselli-Lakhal, Laila

Subjects
MICE, NON-alcoholic fatty liver disease, METABOLIC disorders, FATTY degeneration, FATTY liver, ANDROSTANE receptors, FEMALES, WEIGHT gain
Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease worldwide, affecting 70–90% of obese individuals. In humans, a lower NAFLD incidence is reported in pre-menopausal women, although the mechanisms affording this protection remain under-investigated. Here, we tested the hypothesis that the constitutive androstane nuclear receptor (CAR) plays a role in the pathogenesis of experimental NAFLD. Male and female wild-type (WT) and CAR knock-out (CAR−/−) mice were subjected to a high-fat diet (HFD) for 16 weeks. We examined the metabolic phenotype of mice through body weight follow-up, glucose tolerance tests, analysis of plasmatic metabolic markers, hepatic lipid accumulation, and hepatic transcriptome. Finally, we examined the potential impact of HFD and CAR deletion on specific brain regions, focusing on glial cells. HFD-induced weight gain and hepatic steatosis are more pronounced in WT males than females. CAR−/− females present a NASH-like hepatic transcriptomic signature suggesting a potential NAFLD to NASH transition. Transcriptomic correlation analysis highlighted a possible cross-talk between CAR and ERα receptors. The peripheral effects of CAR deletion in female mice were associated with astrogliosis in the hypothalamus. These findings prove that nuclear receptor CAR may be a potential mechanism entry-point and a therapeutic target for treating NAFLD/NASH. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Effect of Streptomyces roseolus Cell-Free Supernatants on the Fungal Development, Transcriptome, and Aflatoxin B1 Production of Aspergillus flavus.

Author

Maud, Louise, Boyer, Florian, Durrieu, Vanessa, Bornot, Julie, Lippi, Yannick, Naylies, Claire, Lorber, Sophie, Puel, Olivier, Mathieu, Florence, and Snini, Selma P.

Subjects
ASPERGILLUS flavus, AFLATOXINS, STREPTOMYCES, GENE clusters, TRANSCRIPTOMES, BIOLOGICAL pest control agents, BIOACTIVE compounds
Abstract

Crop contamination by aflatoxin B1 (AFB1), an Aspergillus-flavus-produced toxin, is frequently observed in tropical and subtropical regions. This phenomenon is emerging in Europe, most likely as a result of climate change. Alternative methods, such as biocontrol agents (BCAs), are currently being developed to reduce the use of chemicals in the prevention of mycotoxin contamination. Actinobacteria are known to produce many bioactive compounds, and some of them can reduce in vitro AFB1 concentration. In this context, the present study aims to analyze the effect of a cell-free supernatant (CFS) from Streptomyces roseolus culture on the development of A. flavus, as well as on its transcriptome profile using microarray assay and its impact on AFB1 concentration. Results demonstrated that in vitro, the S. roseolus CFS reduced the dry weight and conidiation of A. flavus from 77% and 43%, respectively, and was therefore associated with a reduction in AFB1 concentration reduction to levels under the limit of quantification. The transcriptomic data analysis revealed that 5198 genes were differentially expressed in response to the CFS exposure and among them 5169 were downregulated including most of the genes involved in biosynthetic gene clusters. The aflatoxins' gene cluster was the most downregulated. Other gene clusters, such as the aspergillic acid, aspirochlorine, and ustiloxin B gene clusters, were also downregulated and associated with a variation in their concentration, confirmed by LC-HRMS. [ABSTRACT FROM AUTHOR]

Published
2023
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16. The hepatocyte insulin receptor is required to program the liver clock and rhythmic gene expression

Author

Fougeray, Tiffany, Polizzi, Arnaud, Régnier, Marion, Fougerat, Anne, Ellero-Simatos, Sandrine, Lippi, Yannick, Smati, Sarra, Lasserre, Frédéric, Tramunt, Blandine, Huillet, Marine, Dopavogui, Léonie, Salvi, Juliette, Nédélec, Emmanuelle, Gigot, Vincent, Smith, Lorraine, Naylies, Claire, Sommer, Caroline, Haas, Joel T., Wahli, Walter, Duez, Hélène, Gourdy, Pierre, Gamet-Payrastre, Laurence, Benani, Alexandre, Burnol, Anne-Françoise, Loiseau, Nicolas, Postic, Catherine, Montagner, Alexandra, and Guillou, Hervé

Published
2022
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17. The brlA Gene Deletion Reveals That Patulin Biosynthesis Is Not Related to Conidiation in Penicillium expansum

Author

Zetina-Serrano, Chrystian, Rocher, Ophélie, Naylies, Claire, Lippi, Yannick, Oswald, Isabelle P., Lorber, Sophie, Puel, Olivier, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), 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-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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Transcriptomic impact of Xenobiotics (E23 TRiX), Plateforme Génome & Transcriptome (GET), 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-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), 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)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), ANR-17-CE21-0008,PATRISK,REDUCTION DU RISQUE PATULINE GRACE A UNE GESTION INTEGREE ET DURABLE DE LA PRODUCTION DE POMME ET DE PRODUITS DERIVES(2017), 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
animal structures, Genes, Fungal, Article, Indole Alkaloids, Fungal Proteins, lcsh:Chemistry, synnemata, Gene Expression Regulation, Fungal, Penicillium expansum, lcsh:QH301-705.5, patulin, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, secondary metabolism, brlA, communesins, chaetoglobosins, fungi, Penicillium, food and beverages, conidiogenesis, metabolomics, Biosynthetic Pathways, Up-Regulation, lcsh:Biology (General), lcsh:QD1-999, Fruit, Malus, Multigene Family, Metabolome, Transcriptome, microarray, Gene Deletion
Abstract

Dissemination and survival of ascomycetes is through asexual spores. The brlA gene encodes a C2H2-type zinc-finger transcription factor, which is essential for asexual development. Penicillium expansum causes blue mold disease and is the main source of patulin, a mycotoxin that contaminates apple-based food. A P. expansum Pe&Delta, brlA deficient strain was generated by homologous recombination. In vivo, suppression of brlA completely blocked the development of conidiophores that takes place after the formation of coremia/synnemata, a required step for the perforation of the apple epicarp. Metabolome analysis displayed that patulin production was enhanced by brlA suppression, explaining a higher in vivo aggressiveness compared to the wild type (WT) strain. No patulin was detected in the synnemata, suggesting that patulin biosynthesis stopped when the fungus exited the apple. In vitro transcriptome analysis of Pe&Delta, brlA unveiled an up-regulated biosynthetic gene cluster (PEXP_073960-PEXP_074060) that shares high similarity with the chaetoglobosin gene cluster of Chaetomium globosum. Metabolome analysis of Pe&Delta, brlA confirmed these observations by unveiling a greater diversity of chaetoglobosin derivatives. We observed that chaetoglobosins A and C were found only in the synnemata, located outside of the apple, whereas other chaetoglobosins were detected in apple flesh, suggesting a spatial-temporal organization of the chaetoglobosin biosynthesis pathway.

Published
2020
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18. The GMO90+ Project: Absence of Evidence for Biologically Meaningful Effects of Genetically Modified Maize-based Diets on Wistar Rats After 6-Months Feeding Comparative Trial

Author

Coumoul, Xavier, Servien, Rémi, Juricek, Ludmila, Kaddouch-Amar, Yael, Lippi, Yannick, Berthelot, Laureline, Naylies, Claire, Morvan, Marie-Line, Antignac, Jean-Philippe, Desdoits-Lethimonier, Christèle, Jégou, Bernard, Tremblay-Franco, Marie, Canlet, Cécile, Debrauwer, Laurent, Le Gall, Caroline, Laurent, Julie, Gouraud, Pierre-Antoine, Cravedi, Jean Pierre, Jeunesse, Élisabeth, Savy, Nicolas, Dandere-Abdoulkarim, Kadidiatou, Arnich, Nathalie, Fourès, Franck, Cotton, Jérôme, Broudin, Simon, Corman, Bruno, Moing, Annick, Laporte, Bérengère, RICHARD-FORGET, Florence, Barouki, Robert, Rogowsky, Peter, Salles, Bernard, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Laboratoire de Génétique Cellulaire (LGC), Ecole Nationale Vétérinaire de Toulouse (ENVT), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), 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 ), Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Xénobiotiques, MethodOmics [Toulouse] (Recherche-Développement en Biotechnologie), Methodomics, Laboratoire de sécurité des aliments de Maisons-Alfort, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Profilomic, Biologie du fruit et pathologie (BFP), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1, MycSA, Institut National de la Recherche Agronomique (INRA), CHU Necker - Enfants Malades [AP-HP], Reproduction et développement des plantes (RDP), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Coumoul, Xavier, 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, Transcriptomic impact of Xenobiotics (E23 TRiX), 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-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), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), 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 de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaboHUB-MetaToul, Direction de l'Evaluation des Risques (DER), Profilomic [Boulogne-Billancourt], Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB), Unité de recherche Mycologie et Sécurité des Aliments (MycSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Université de Toulouse (UT)-Université de Toulouse (UT)-Plateforme Génome & Transcriptome (GET), 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)-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)-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 AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-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)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), 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-Institut National de la Recherche Agronomique (INRA), Centre de recherche sur l'Inflammation (CRI), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche, santé, environnement et travail (Irset), 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), Institut de Mathématiques de Toulouse UMR5219 (IMT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-PRES Université de Toulouse-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), ANSES - Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, 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 Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDE] Environmental Sciences, genetically modified maize, OECD TG408, Male, [SDV]Life Sciences [q-bio], Food, Genetically Modified, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Zea mays, MON810, transcriptomics, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Toxicity Tests, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Animals, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Rats, Wistar, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, 6-month rat feeding trial, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Plants, Genetically Modified, [SDE.ES]Environmental Sciences/Environmental and Society, metabolomics, Animal Feed, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], NK603, Rats, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Consumer Product Safety, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDE]Environmental Sciences, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Safety Study of Gmo Maize, Female, [SDE.ES] Environmental Sciences/Environmental and Society, Edible Grain
Abstract

International audience; The GMO90+ project was designed to identify biomarkers of exposure or health effects in Wistar Han RCC rats exposed in their diet to 2 genetically modified plants (GMP) and assess additional information with the use of metabolomic and transcriptomic techniques. Rats were fed for 6-months with 8 maize-based diets at 33% that comprised either MON810 (11% and 33%) or NK603 grains (11% and 33% with or without glyphosate treatment) or their corresponding near-isogenic controls. Extensive chemical and targeted analyses undertaken to assess each diet demonstrated that they could be used for the feeding trial. Rats were necropsied after 3 and 6 months. Based on the Organization for Economic Cooperation and Development test guideline 408, the parameters tested showed a limited number of significant differences in pairwise comparisons, very few concerning GMP versus non-GMP. In such cases, no biological relevance could be established owing to the absence of difference in biologically linked variables, dose-response effects, or clinical disorders. No alteration of the reproduction function and kidney physiology was found. Metabolomics analyses on fluids (blood, urine) were performed after 3, 4.5, and 6 months. Transcriptomics analyses on organs (liver, kidney) were performed after 3 and 6 months. Again, among the significant differences in pairwise comparisons, no GMP effect was observed in contrast to that of maize variety and culture site. Indeed, based on transcriptomic and metabolomic data, we could differentiate MON- to NK-based diets. In conclusion, using this experimental design, no biomarkers of adverse health effect could be attributed to the consumption of GMP diets in comparison with the consumption of their near-isogenic non-GMP controls.

Published
2018
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19. Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target.

Author

Smati, Sarra, Polizzi, Arnaud, Fougerat, Anne, Ellero-Simatos, Sandrine, Blum, Yuna, Lippi, Yannick, Régnier, Marion, Laroyenne, Alexia, Huillet, Marine, Arif, Muhammad, Cheng Zhang, Lasserre, Frederic, Marrot, Alain, Al Saati, Talal, JingHong Wan, Sommer, Caroline, Naylies, Claire, Batut, Aurelie, Lukowicz, Celine, and Fougeray, Tiffany

Subjects
FATTY liver, CHOLESTEROL content of food, NON-alcoholic fatty liver disease, ELLAGIC acid, DRUG target, SEXUAL dimorphism, LABORATORY mice, NF-kappa B
Published
2022
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20. Sex dimorphic role of estrogen receptor a in physiological regulation of hepatic metabolism

Author

Tramunt, Blandine, SMATI, Sarra, Grandgeorge, Naia, Fougerat, Anne, Guillaume, Maxime, Arnal, Jean-François, Naylies, Claire, Lippi, Yannick, Guillou, Hervé, Montagner, Alexandra, Gourdy, Pierre, ProdInra, Migration, CHU Toulouse [Toulouse], 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), 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), 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), Transcriptomic impact of Xenobiotics (E23 TRiX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), 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)-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 Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), 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-Plateforme Génome & Transcriptome (GET), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

22. Impact of veA on the development, aggressiveness, dissemination and secondary metabolism of Penicillium expansum

Author

El Hajj Assaf, Christelle, Snini, Selma, Tadrist, Souria, Bally, Sylviane, Naylies, Claire, Oswald, Isabelle P., Lorber, Sophie, Puel, Olivier, Flanders Research Institute for agriculture, fisheries and food - ILVO (BELGIUM), Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut National de la Recherche Agronomique - INRA (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), 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), Flanders Research Institute for Agriculture, Fisheries and Food (ILVO), Research Institute for Agricultural, Fisheries and Food (ILVO), Transcriptomic impact of Xenobiotics (E23 TRiX), 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)-Plateforme Génome & Transcriptome (GET), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), CASDAR AAP RT 2015 under Grant 1508 and by French National Research Agency under Grant ANR-17-CE21-0008 PATRISK, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), 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-Plateforme Génome & Transcriptome (GET), 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)-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 Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)

Subjects
Patulin, Apples, Penicilium expansum, food and beverages, Pathogenicity, Biologie cellulaire, Original Articles, Secondary metabolism, veA, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Citrinin
Abstract

International audience; Penicillium expansum, the causal agent of blue mould disease, produces the mycotoxins patulin and citrinin amongst other secondary metabolites. Secondary metabolism is associated with fungal development, which responds to numerous biotic and abiotic external triggers. The global transcription factor VeA plays a key role in the coordination of secondary metabolism and differentiation processes in many fungal species. The specific role of VeA in P. expansum remains unknown. A null mutant PeΔveA strain and a complemented PeΔveA:veA strain were generated in P. expansum and their pathogenicity on apples was studied. Like the wild‐type and the complemented strains, the null mutant PeΔveA strain was still able to sporulate and to colonize apples, but at a lower rate. However, it could not form coremia either in vitro or in vivo, thus limiting its dissemination from natural substrates. The impact of veA on the expression of genes encoding proteins involved in the production of patulin, citrinin and other secondary metabolites was evaluated. The disruption of veA drastically reduced the production of patulin and citrinin on synthetic media, associated with a marked down‐regulation of all genes involved in the biosynthesis of the two mycotoxins. Moreover, the null mutant PeΔveA strain was unable to produce patulin on apples. The analysis of gene expression revealed a global impact on secondary metabolism, as 15 of 35 backbone genes showed differential regulation on two different media. These findings support the hypothesis that VeA contributes to the pathogenicity of P. expansum and modulates its secondary metabolism.

Published
2018
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23. Metabolic Effects of a Chronic Dietary Exposure to a Low-Dose Pesticide Cocktail in Mice: Sexual Dimorphism and Role of the Constitutive Androstane Receptor

Author

Lukowicz, Celine, Ellero-Simatos, Sandrine, Regnier, Marion, Polizzi, Arnaud, Lasserre, Frederic, Montagner, Alexandra, Lippi, Yannick, Jamin, Emilien L., Martin, Jean- Francois, Naylies, Claire, Canle, Cecile, Debrauwer, Laurent, Bertrand-Michel, Justine, Saati, Talal Al, Theodorou, Vassilia, Loiseau, Nicolas, Mselli-Lakhal, Laila, Guillou, Herve, and Gamet-Payrastre, Laurence

Subjects
European Union. European Food Safety Authority, Care and treatment, Usage, Research, Genetic aspects, Health aspects, Metabolites -- Research, Metabolic diseases -- Genetic aspects -- Care and treatment -- Research, Liquid chromatography -- Usage, Body weight -- Physiological aspects -- Health aspects, Mass spectrometry -- Usage
Abstract

Introduction The rates of metabolic disorders, including obesity and its complications, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD), have increased dramatically over the past three [...], BACKGROUND: Epidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at nonrelevant doses or in combination with other risk factors such as high-fat diets. OBJECTIVES: We aimed to evaluate, in mice, the metabolic consequences of chronic dietary exposure to a pesticide mixture at nontoxic doses, relevant to consumers' risk assessment. METHODS: A mixture of six pesticides commonly used in France, i.e., boscalid, captan, chlorpyrifos, thiofanate, thiacloprid, and ziram, was incorporated in a standard chow at doses exposing mice to the tolerable daily intake (TDI) of each pesticide. Wild-type (WT) and constitutive androstane receptor-deficient ([CAR.sup.-/-]) male and female mice were exposed for 52 wk. We assessed metabolic parameters [body weight (BW), food and water consumption, glucose tolerance, urinary metabolome] throughout the experiment. At the end of the experiment, we evaluated liver metabolism (histology, transcriptomics, metabolomics, lipidomics) and pesticide detoxification using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Compared to those fed control chow, WT male mice fed pesticide chow had greater BW gain and more adiposity. Moreover, these WT males fed pesticide chow exhibited characteristics of hepatic steatosis and glucose intolerance, which were not observed in those fed control chow. WT exposed female mice exhibited fasting hyperglycemia, higher reduced glutathione (GSH):oxidized glutathione (GSSG) liver ratio and perturbations of gut microbiota-related urinary metabolites compared to WT mice fed control chow. When we performed these experiments on [CAR.sup.-/-] mice, pesticide-exposed [CAR.sup.-/-] males did not exhibit BW gain or changes in glucose metabolism compared to the [CAR.sup.-/-] males fed control chow. Moreover, [CAR.sup.-/-] females fed pesticide chow exhibited pesticide toxicity with higher BWs and mortality rate compared to the [CAR.sup.-/-] females fed control chow. CONCLUSIONS: To our knowledge, we are the first to demonstrate a sexually dimorphic obesogenic and diabetogenic effect of chronic dietary exposure to a common mixture of pesticides at TDI levels, and to provide evidence for a partial role for CAR in an in vivo mouse model. This raises questions about the relevance of TDI for individual pesticides when present in a mixture. https://doi.org/10.1289/EHP2877

Published
2018
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24. Hepatocyte-specific deletion of Pparα promotes NAFLD in the context of obesity.

Author

Régnier, Marion, Polizzi, Arnaud, Smati, Sarra, Lukowicz, Céline, Fougerat, Anne, Lippi, Yannick, Fouché, Edwin, Lasserre, Frédéric, Naylies, Claire, Bétoulières, Colette, Barquissau, Valentin, Mouisel, Etienne, Bertrand-Michel, Justine, Batut, Aurélie, Saati, Talal Al, Canlet, Cécile, Tremblay-Franco, Marie, Ellero-Simatos, Sandrine, Langin, Dominique, and Postic, Catherine

Subjects
LIVER cells, FATTY liver, PUBLIC health, HOMEOSTASIS, OBESITY, HIGH-fat diet
Abstract

Peroxisome proliferator activated receptor α (PPARα) acts as a fatty acid sensor to orchestrate the transcription of genes coding for rate-limiting enzymes required for lipid oxidation in hepatocytes. Mice only lacking Pparα in hepatocytes spontaneously develop steatosis without obesity in aging. Steatosis can develop into non alcoholic steatohepatitis (NASH), which may progress to irreversible damage, such as fibrosis and hepatocarcinoma. While NASH appears as a major public health concern worldwide, it remains an unmet medical need. In the current study, we investigated the role of hepatocyte PPARα in a preclinical model of steatosis. For this, we used High Fat Diet (HFD) feeding as a model of obesity in C57BL/6 J male Wild-Type mice (WT), in whole-body Pparα- deficient mice (Pparα−/−) and in mice lacking Pparα only in hepatocytes (Pparαhep−/−). We provide evidence that Pparα deletion in hepatocytes promotes NAFLD and liver inflammation in mice fed a HFD. This enhanced NAFLD susceptibility occurs without development of glucose intolerance. Moreover, our data reveal that non-hepatocytic PPARα activity predominantly contributes to the metabolic response to HFD. Taken together, our data support hepatocyte PPARα as being essential to the prevention of NAFLD and that extra-hepatocyte PPARα activity contributes to whole-body lipid homeostasis. [ABSTRACT FROM AUTHOR]

Published
2020
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25. The GMO90+ Project: Absence of Evidence for Biologically Meaningful Effects of Genetically Modified Maize-based Diets on Wistar Rats After 6-Months Feeding Comparative Trial.

Author

Coumoul, Xavier, Servien, Rémi, Juricek, Ludmila, Kaddouch-Amar, Yael, Lippi, Yannick, Berthelot, Laureline, Naylies, Claire, Morvan, Marie-Line, Antignac, Jean-Philippe, Desdoits-Lethimonier, Christèle, Jegou, Bernard, Tremblay-Franco, Marie, Canlet, Cécile, Debrauwer, Laurent, Gall, Caroline Le, Laurent, Julie, Gouraud, Pierre-Antoine, Cravedi, Jean-Pierre, Jeunesse, Elisabeth, and Savy, Nicolas

Subjects
TRANSGENIC plants, ANIMAL feeding, KIDNEY physiology, RATS, INTERNATIONAL economic relations
Abstract

The GMO90+ project was designed to identify biomarkers of exposure or health effects in Wistar Han RCC rats exposed in their diet to 2 genetically modified plants (GMP) and assess additional information with the use of metabolomic and transcriptomic techniques. Rats were fed for 6-months with 8 maize-based diets at 33% that comprised either MON810 (11% and 33%) or NK603 grains (11% and 33% with or without glyphosate treatment) or their corresponding near-isogenic controls. Extensive chemical and targeted analyses undertaken to assess each diet demonstrated that they could be used for the feeding trial. Rats were necropsied after 3 and 6 months. Based on the Organization for Economic Cooperation and Development test guideline 408, the parameters tested showed a limited number of significant differences in pairwise comparisons, very few concerning GMP versus non-GMP. In such cases, no biological relevance could be established owing to the absence of difference in biologically linked variables, dose-response effects, or clinical disorders. No alteration of the reproduction function and kidney physiology was found. Metabolomics analyses on fluids (blood, urine) were performed after 3, 4.5, and 6 months. Transcriptomics analyses on organs (liver, kidney) were performed after 3 and 6 months. Again, among the significant differences in pairwise comparisons, no GMP effect was observed in contrast to that of maize variety and culture site. Indeed, based on transcriptomic and metabolomic data, we could differentiate MON- to NK-based diets. In conclusion, using this experimental design, no biomarkers of adverse health effect could be attributed to the consumption of GMP diets in comparison with the consumption of their near-isogenic non-GMP controls. [ABSTRACT FROM AUTHOR]

Published
2019
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26. The GeT-TRiX facility: automated processing of expression microarrays - from samples to data analysis reports

Author

Lippi, Yannick, Naylies, Claire, Martin, Pascal G.P., Transcriptomic impact of Xenobiotics (E23 TRiX), 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-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, 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), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

27. Time course study of the response to LPS targeting the pig immune gene networks.

Author

Terenina, Elena, Sautron, Valérie, Ydier, Caroline, Bazovkina, Darya, Sevin-Pujol, Amélie, Gress, Laure, Lippi, Yannick, Naylies, Claire, Billon, Yvon, Liaubet, Laurence, Mormede, Pierre, and Villa-Vialaneix, Nathalie

Subjects
HYDROCORTISONE, HYPOTHALAMIC-pituitary-adrenal axis, LIPOPOLYSACCHARIDES, LEUKOCYTES, ROBUST control
Abstract

Background: Stress is a generic term used to describe non-specific responses of the body to all kinds of challenges. A very large variability in the response can be observed across individuals, depending on numerous conditioning factors like genetics, early influences and life history. As a result, there is a wide range of individual vulnerability and resilience to stress, also called robustness. The importance of robustness-related traits in breeding strategies is increasing progressively towards the production of animals with a high level of production under a wide range of climatic conditions and management systems, together with a lower environmental impact and a high level of animal welfare. The present study aims at describing blood transcriptomic, hormonal, and metabolic responses of pigs to a systemic challenge using lipopolysaccharide (LPS). The objective is to analyze the individual variation of the biological responses in relation to the activity of the HPA axis measured by the levels of plasma cortisol after LPS and ACTH in 120 juvenile Large White (LW) pigs. The kinetics of the response was measured with biological variables and whole blood gene expression at 4 time points. A multilevel statistical analysis was used to take into account the longitudinal aspect of the data. Results: Cortisol level reaches its peak 4 h after LPS injection. The characteristic changes of white blood cell count to LPS were observed, with a decrease of total count, maximal at t = +4 h, and the mirror changes in the respective proportions of lymphocytes and granulocytes. The lymphocytes / granulocytes ratio was maximal at t = +1 h. An integrative statistical approach was used and provided a set of candidate genes for kinetic studies and ongoing complementary studies focused on the LPS-stimulated inflammatory response. Conclusions: The present study demonstrates the specific biomarkers indicative of an inflammation in swine. Furthermore, these stress responses persist for prolonged periods of time and at significant expression levels, making them good candidate markers for evaluating the efficacy of anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Published
2017
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28. Deciphering the Anti-Aflatoxinogenic Properties of Eugenol Using a Large-Scale q-PCR Approach.

Author

Caceres, Isaura, El Khoury, Rhoda, Medina, Ángel, Lippi, Yannick, Naylies, Claire, Atoui, Ali, El Khoury, André, Oswald, Isabelle P., Bailly, Jean-Denis, and Puel, Olivier

Subjects
AFLATOXINS, EUGENOL, ASPERGILLUS, FUNGICIDES, MYCOTOXINS, BIOSYNTHESIS
Abstract

Produced by several species of Aspergillus, Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin contaminating many crops worldwide. The utilization of fungicides is currently one of the most common methods; nevertheless, their use is not environmentally or economically sound. Thus, the use of natural compounds able to block aflatoxinogenesis could represent an alternative strategy to limit food and feed contamination. For instance, eugenol, a 4-allyl-2-methoxyphenol present in many essential oils, has been identified as an anti-aflatoxin molecule. However, its precise mechanism of action has yet to be clarified. The production of AFB1 is associated with the expression of a 70 kB cluster, and not less than 21 enzymatic reactions are necessary for its production. Based on former empirical data, a molecular tool composed of 60 genes targeting 27 genes of aflatoxin B1 cluster and 33 genes encoding the main regulatory factors potentially involved in its production, was developed. We showed that AFB1 inhibition in Aspergillus flavus following eugenol addition at 0.5 mM in a Malt Extract Agar (MEA) medium resulted in a complete inhibition of the expression of all but one gene of the AFB1 biosynthesis cluster. This transcriptomic effect followed a down-regulation of the complex composed by the two internal regulatory factors, AflR and AflS. This phenomenon was also influenced by an over-expression of veA and mtfA, two genes that are directly linked to AFB1 cluster regulation. [ABSTRACT FROM AUTHOR]

Published
2016
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29. Tissular Genomic Responses to Oral FB1 Exposure in Pigs.

Author

Dopavogui, Léonie, Polizzi, Arnaud, Fougerat, Anne, Gourbeyre, Pascal, Terciolo, Chloé, Klement, Wendy, Pinton, Philippe, Laffite, Joëlle, Cossalter, Anne-Marie, Bailly, Jean-Denis, Puel, Olivier, Lippi, Yannick, Naylies, Claire, Guillou, Hervé, Oswald, Isabelle P., and Loiseau, Nicolas

Subjects
CELL cycle regulation, SWINE, FUMONISINS, EXTRACELLULAR matrix, CELL migration, ANIMAL species, JEJUNUM
Abstract

Fumonisin B1 (FB1) is a widespread mycotoxin produced by fungal Fusarium species—mainly in maize, one of the plants most commonly used for food and feed. Pigs and horses are the animal species most susceptible to this mycotoxin. FB1 exposure can cause highly diverse clinical symptoms, including hepatotoxicity, immunotoxicity, and intestinal barrier function disturbance. Inhibition of ceramide synthetase is a well-understood ubiquitous molecular mechanism of FB1 toxicity, but other more tissue-specific effects remain to be elucidated. To investigate the effects of FB1 in different exposed tissues, we cross-analyzed the transcriptomes of fours organs: liver, jejunum, jejunal Peyer's patches, and spleen. During a four-week study period, pigs were fed a control diet or a FB1-contaminated diet (10 mg/kg feed). In response to oral FB1 exposure, we observed common biological processes in the four organs, including predominant and recurrent processes (extracellular matrix organization, integrin activation, granulocyte chemotaxis, neutrophil migration, and lipid and sterol homeostasis), as well as more tissue-specific processes that appeared to be related to lipid outcomes (cell cycle regulation in jejunum, and gluconeogenesis in liver). [ABSTRACT FROM AUTHOR]

Published
2022
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30. The Solvent Dimethyl Sulfoxide Affects Physiology, Transcriptome and Secondary Metabolism of Aspergillus flavus.

Author

Costes, Laura H., Lippi, Yannick, Naylies, Claire, Jamin, Emilien L., Genthon, Clémence, Bailly, Sylviane, Oswald, Isabelle P., Bailly, Jean-Denis, and Puel, Olivier

Subjects
DIMETHYL sulfoxide, TRANSCRIPTOMES, SECONDARY metabolism, ASPERGILLUS flavus, FOOD safety
Abstract

Dimethyl sulfoxide (DSMO) is a simple molecule widely used because of its great solvating ability, but this solvent also has little-known biological effects, especially on fungi. Aspergillus flavus is a notorious pathogenic fungus which may contaminate a large variety of crops worldwide by producing aflatoxins, endangering at the same time food safety and international trade. The aim of this study was to characterize the effect of DMSO on A. flavus including developmental parameters such as germination and sporulation, as well as its transcriptome profile using high-throughput RNA-sequencing assay and its impact on secondary metabolism (SM). After DMSO exposure, A. flavus displayed depigmented conidia in a dose-dependent manner. The four-day exposition of cultures to two doses of DMSO, chosen on the basis of depigmentation intensity (35 mM "low" and 282 mM "high"), led to no significant impact on fungal growth, germination or sporulation. However, transcriptomic data analysis showed that 4891 genes were differentially regulated in response to DMSO (46% of studied transcripts). A total of 4650 genes were specifically regulated in response to the highest dose of DMSO, while only 19 genes were modulated upon exposure to the lowest dose. Secondary metabolites clusters genes were widely affected by the DMSO, with 91% of clusters impacted at the highest dose. Among these, aflatoxins, cyclopiazonic acid and ustiloxin B clusters were totally under-expressed. The genes belonging to the AFB1 cluster were the most negatively modulated ones, the two doses leading to 63% and 100% inhibition of the AFB1 production, respectively. The SM analysis also showed the disappearance of ustiloxin B and a 10-fold reduction of cyclopiazonic acid level when A. flavus was treated by the higher DMSO dose. In conclusion, the present study showed that DMSO impacted widely A. flavus' transcriptome, including secondary metabolism gene clusters with the aflatoxins at the head of down-regulated ones. The solvent also inhibits conidial pigmentation, which could illustrate common regulatory mechanisms between aflatoxins and fungal pigment pathways. Because of its effect on major metabolites synthesis, DMSO should not be used as solvent especially in studies testing anti-aflatoxinogenic compounds. [ABSTRACT FROM AUTHOR]

Published
2021
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31. Statistical Integration of 'Omics Data Increases Biological Knowledge Extracted from Metabolomics Data: Application to Intestinal Exposure to the Mycotoxin Deoxynivalenol.

Author

Tremblay-Franco, Marie, Canlet, Cécile, Pinton, Philippe, Lippi, Yannick, Gautier, Roselyne, Naylies, Claire, Neves, Manon, Oswald, Isabelle P., Debrauwer, Laurent, and Alassane-Kpembi, Imourana

Subjects
DEOXYNIVALENOL, INTESTINES, METABOLOMICS, SELF-organizing maps, PROTEIN synthesis, ENERGY metabolism, INFLAMMASOMES
Abstract

The effects of low doses of toxicants are often subtle and information extracted from metabolomic data alone may not always be sufficient. As end products of enzymatic reactions, metabolites represent the final phenotypic expression of an organism and can also reflect gene expression changes caused by this exposure. Therefore, the integration of metabolomic and transcriptomic data could improve the extracted biological knowledge on these toxicants induced disruptions. In the present study, we applied statistical integration tools to metabolomic and transcriptomic data obtained from jejunal explants of pigs exposed to the food contaminant, deoxynivalenol (DON). Canonical correlation analysis (CCA) and self-organizing map (SOM) were compared for the identification of correlated transcriptomic and metabolomic features, and O2-PLS was used to model the relationship between exposure and selected features. The integration of both 'omics data increased the number of discriminant metabolites discovered (39) by about 10 times compared to the analysis of the metabolomic dataset alone (3). Besides the disturbance of energy metabolism previously reported, assessing correlations between both functional levels revealed several other types of damage linked to the intestinal exposure to DON, including the alteration of protein synthesis, oxidative stress, and inflammasome activation. This confirms the added value of integration to enrich the biological knowledge extracted from metabolomics. [ABSTRACT FROM AUTHOR]

Published
2021
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32. Gene Expression Profiling Reveals that PXR Activation Inhibits Hepatic PPARα Activity and Decreases FGF21 Secretion in Male C57Bl6/J Mice.

Author

Barretto, Sharon Ann, Lasserre, Frédéric, Fougerat, Anne, Smith, Lorraine, Fougeray, Tiffany, Lukowicz, Céline, Polizzi, Arnaud, Smati, Sarra, Régnier, Marion, Naylies, Claire, Bétoulières, Colette, Lippi, Yannick, Guillou, Hervé, Loiseau, Nicolas, Gamet-Payrastre, Laurence, Mselli-Lakhal, Laila, and Ellero-Simatos, Sandrine

Subjects
GENE expression profiling, PREGNANE X receptor, NUCLEAR receptors (Biochemistry), PROTEIN expression, HOMEOSTASIS, PEROXISOME proliferator-activated receptors, FIBROBLAST growth factors, TRANSCRIPTOMES, SECRETION, MICE, GENE expression
Abstract

The article examines the transcriptomic signature of pregnane X receptor (PXR) activation in the liver of adult wild-type vs. Pxr -/- C57BI6/J male mice treated with the rodent specific ligand pregnenolone 16-carbonitrile. Topics covered include potential metabolic dysregulations induced upon PXR activation, effect of PXR activation on physiological parameters and liver lipids, and the effects of PXR activation on the hepatic transcriptome.

Published
2019
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33. A Genome-Wide Association Study Points out the Causal Implication of SOX9 in the Sex-Reversal Phenotype in XX Pigs.

Author

Rousseau, Sarah, Iannuccelli, Nathalie, Mercat, Marie-José, Naylies, Claire, Thouly, Jean-Claude, Servin, Bertrand, Milan, Denis, Pailhoux, Eric, and Riquet, Juliette

Subjects
SEX change in animals, INTERSEXUALITY, LABORATORY swine, CONGENITAL heart disease, ECONOMIC equilibrium, SEX differentiation (Embryology)
Abstract

Among farm animals, pigs are known to show XX sex-reversal. In such cases the individuals are genetically female but exhibit a hermaphroditism, or a male phenotype. While the frequency of this congenital disease is quite low (less than 1%), the economic losses are significant for pig breeders. These losses result from sterility, urogenital infections and the carcasses being downgraded because of the risk of boar taint. It has been clearly demonstrated that the SRY gene is not involved in most cases of sex-reversal in pigs, and that autosomal recessive mutations remain to be discovered. A whole-genome scan analysis was performed in the French Large-White population to identify candidate genes: 38 families comprising the two non-affected parents and 1 to 11 sex-reversed full-sib piglets were genotyped with the PorcineSNP60 BeadChip. A Transmission Disequilibrium Test revealed a highly significant candidate region on SSC12 (most significant p-value<4.65.10-10) containing the SOX9 gene. SOX9, one of the master genes involved in testis differentiation, was sequenced together with one of its main regulatory region Tesco. However, no causal mutations could be identified in either of the two sequenced regions. Further haplotype analyses did not identify a shared homozygous segment between the affected pigs, suggesting either a lack of power due to the SNP properties of the chip, or a second causative locus. Together with information from humans and mice, this study in pigs adds to the field of knowledge, which will lead to characterization of novel molecular mechanisms regulating sexual differentiation and dysregulation in cases of sex reversal. [ABSTRACT FROM AUTHOR]

Published
2013
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34. Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways.

Author

Alassane-Kpembi I, Gerez JR, Cossalter AM, Neves M, Laffitte J, Naylies C, Lippi Y, Kolf-Clauw M, Bracarense APL, Pinton P, and Oswald IP

Subjects
Animals, Castration, Cell Line, Epithelial Cells cytology, Epithelial Cells drug effects, Epithelial Cells metabolism, Fusarium chemistry, Fusarium pathogenicity, Gene Expression Profiling, Jejunum cytology, Jejunum metabolism, Lipid Metabolism drug effects, Liver X Receptors genetics, Liver X Receptors metabolism, Male, Microarray Analysis, Mycotoxins isolation & purification, Peroxisome Proliferator-Activated Receptors genetics, Peroxisome Proliferator-Activated Receptors metabolism, Receptors, Calcitriol genetics, Receptors, Calcitriol metabolism, Retinoid X Receptors genetics, Retinoid X Receptors metabolism, Signal Transduction genetics, Swine, Tissue Culture Techniques, Trichothecenes isolation & purification, Gene Expression Regulation drug effects, Jejunum drug effects, Mycotoxins toxicity, Signal Transduction drug effects, Transcriptome drug effects, Trichothecenes toxicity
Abstract

The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins. The benchmark doses for the up-regulation of key inflammatory genes by FX were 4- to 45-fold higher than the previously reported values for DON. The transcriptome analysis revealed that both mycotoxins down-regulated the peroxisome proliferator-activated receptor (PPAR) and liver X receptor - retinoid X receptor (LXR-RXR) signaling pathways that control lipid metabolism. Interestingly, several pathways, including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling, were specific to FX and thus discriminated the transcriptomic fingerprints of the two mycotoxins. These results demonstrate that FX induces more potent intestinal inflammation than DON. Moreover, although the mechanisms of toxicity of both mycotoxins are similar in many ways, this study emphasize specific pathways targeted by each mycotoxin, highlighting the need for specific mechanism-based risk assessments of Fusarium mycotoxins.

Published
2017
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