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125 results on '"Métabolisme et Xénobiotiques (ToxAlim-MeX)"'

1. Development of new approach methods for the identification and characterization of endocrine metabolic disruptors : a PARC project

Author: Braeuning, Albert, Balaguer, Patrick, Bourguet, William, Carreras-Puigvert, Jordi, Feiertag, Katreece, Kamstra, Jorke, Knapen, Dries, Lichtenstein, Dajana, Marx-Stoelting, Philip, Rietdijk, Jonne, Schubert, Kristin, Spjuth, Ola, Stinckens, Evelyn, Thedieck, Kathrin, van den Boom, Rik, Vergauwen, Lucia, von Bergen, Martin, Wewer, Neele, Zalko, Daniel, German Federal Institute for Risk Assessment [Berlin] (BfR), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Biologie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Uppsala University, Utrecht University [Utrecht], University of Antwerp (UA), Uppsala Universitet [Uppsala], Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Universität Innsbruck [Innsbruck], Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by Horizon Europe, the European Union’s 2021–2027 framework program for the funding of research and innovation under der grant agreement No. 101057014 (project PARC). Additional co-funding of the University of Antwerp Research Fund through a GOA project (FFB180348/36572) is acknowledged., and European Project: 101057014,Horizon Europe,PARC(2022)
Subjects: Chemistry, adipocytes, [SDV]Life Sciences [q-bio], Veterinary medicine, energy metabolism, nuclear receptors, obesogens, endocrine metabolic disruption, liver
Abstract: International audience; In past times, the analysis of endocrine disrupting properties of chemicals has mainly been focused on (anti-)estrogenic or (anti-)androgenic properties, as well as on aspects of steroidogenesis and the modulation of thyroid signaling. More recently, disruption of energy metabolism and related signaling pathways by exogenous substances, so-called metabolism-disrupting chemicals (MDCs) have come into focus. While general effects such as body and organ weight changes are routinely monitored in animal studies, there is a clear lack of mechanistic test systems to determine and characterize the metabolism-disrupting potential of chemicals. In order to contribute to filling this gap, one of the project within EU-funded Partnership for the Assessment of Risks of Chemicals (PARC) aims at developing novel in vitro methods for the detection of endocrine metabolic disruptors. Efforts will comprise projects related to specific signaling pathways, for example, involving mTOR or xenobiotic-sensing nuclear receptors, studies on hepatocytes, adipocytes and pancreatic beta cells covering metabolic and morphological endpoints, as well as metabolism-related zebrafish-based tests as an alternative to classic rodent bioassays. This paper provides an overview of the approaches and methods of these PARC projects and how this will contribute to the improvement of the toxicological toolbox to identify substances with endocrine disrupting properties and to decipher their mechanisms of action.
Published: 2023

2. Milk metabolome reveals variations on enteric methane emissions from dairy cows fed a specific inhibitor of the methanogenesis pathway

Author: Diego P. Morgavi, Hamid Boudra, Bénédict Yanibada, Stéphanie Durand, Ulli Hohenester, Fabien Jourdan, Cécile Canlet, Anne Ferlay, Mélanie Pétéra, LESUR, Hélène, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme Exploration du Métabolisme-MetaboHUB (PFEM-MetaboHUB), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), 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), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, 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)-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), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, 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), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, 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 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)-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)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: Rumen, multiplatform metabolomics, [SDV.BA] Life Sciences [q-bio]/Animal biology, Methanogenesis, [SDV]Life Sciences [q-bio], Gas Chromatography-Mass Spectrometry, 03 medical and health sciences, Metabolomics, Lactation, Genetics, Metabolome, medicine, Animals, [SDV.SA.SPA] Life Sciences [q-bio]/Agricultural sciences/Animal production studies, Food science, microbial metabolite, 030304 developmental biology, 2. Zero hunger, milk, 0303 health sciences, methane biomarker, Chemistry, dairy cow, [SDV.BA]Life Sciences [q-bio]/Animal biology, 0402 animal and dairy science, 04 agricultural and veterinary sciences, Metabolism, 040201 dairy & animal science, Diet, [SDV] Life Sciences [q-bio], Metabolic pathway, medicine.anatomical_structure, 13. Climate action, [SDV.SA.SPA]Life Sciences [q-bio]/Agricultural sciences/Animal production studies, Fermentation, Cattle, Female, Animal Science and Zoology, Gas chromatography, Methane, Food Science
Abstract: International audience; Metabolome profiling in biological fluids is an interesting approach for exploring markers of methane emissions in ruminants. In this study, a multiplatform metabolomics approach was used for investigating changes in milk metabolic profiles related to methanogenesis in dairy cows. For this purpose, 25 primiparous Holstein cows at similar lactation stage were fed the same diet supplemented with (treated, n = 12) or without (control, n = 13) a specific antimethanogenic additive that reduced enteric methane production by 23% with no changes in intake, milk production, and health status. The study lasted 6 wk, with sampling and measures performed in wk 5 and 6. Milk samples were analyzed using 4 complementary analytical methods, including 2 untargeted (nuclear magnetic resonance and liquid chromatography coupled to a quadrupole-time-of-flight mass spectrometer) and 2 targeted (liquid chromatography-tandem mass spectrometry and gas chromatography coupled to a flame ionization detector) approaches. After filtration, variable selection and normalization data from each analytical platform were then analyzed using multivariate orthogonal partial least square discriminant analysis. All 4 analytical methods were able to differentiate cows from treated and control groups. Overall, 38 discriminant metabolites were identified, which affected 10 metabolic pathways including methane metabolism. Some of these metabolites such as dimethylsulfoxide, dimethylsulfone, and citramalic acid, detected by nuclear magnetic resonance or liquid chromatography-mass spectrometry methods, originated from the rumen microbiota or had a microbial-host animal co-metabolism that could be associated with methanogenesis. Also, discriminant milk fatty acids detected by targeted gas chromatography were mostly of ruminal microbial origin. Other metabolites and metabolic pathways significantly affected were associated with AA metabolism. These findings provide new insight on the potential role of milk metabolites as indicators of enteric methane modifications in dairy cows.
Published: 2021

3. Gestational exposure to bisphenol A induces region-specific changes in brain metabolomic fingerprints in sheep

Author: Davy Guignard, Cécile Canlet, Marie Tremblay-Franco, Elodie Chaillou, Roselyne Gautier, Véronique Gayrard, Nicole Picard-Hagen, Henri Schroeder, Fabien Jourdan, Daniel Zalko, Catherine Viguié, Nicolas J. Cabaton, 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), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, 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)-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), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), 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), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), 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), Métabolisme et Xénobiotiques (ToxAlim-MeX), Davy Guignard received a PhD grand from the Doctoral School 'SEVAB' of the university Paul Sabatier of Toulouse, France., ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), LESUR, Hélène, and Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID
Subjects: endocrine system, Sheep, [SDV]Life Sciences [q-bio], Neurodevelopment, Brain, Metabolomic, Endocrine Disruptors, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, Mice, Bisphenol A, Phenols, Maternal Exposure, Pregnancy, Prenatal Exposure Delayed Effects, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Animals, Humans, Female, Benzhydryl Compounds, Fetal exposure, General Environmental Science, Environmental contaminants
Abstract: International audience; Fetal brain development depends on maternofetal thyroid function. In rodents and sheep, perinatal BPA exposure is associated with maternal and/or fetal thyroid disruption and alterations in central nervous system development as demonstrated by metabolic modulations in the encephala of mice. We hypothesized that a gestational exposure to a low dose of BPA affects maternofetal thyroid function and fetal brain development in a region-specific manner. Pregnant ewes, a relevant model for human thyroid and brain development, were exposed to BPA (5 µg/kg bw/d, sc). The thyroid status of ewes during gestation and term fetuses at delivery was monitored. Fetal brain development was assessed by metabolic fingerprints at birth in 10 areas followed by metabolic network-based analysis. BPA treatment was associated with a significant time-dependent decrease in maternal TT4 serum concentrations. For 8 fetal brain regions, statistical models allowed discriminating BPA-treated from control lambs. Metabolic network computational analysis revealed that prenatal exposure to BPA modulated several metabolic pathways, in particular excitatory and inhibitory amino-acid, cholinergic, energy and lipid homeostasis pathways. These pathways might contribute to BPA-related neurobehavioral and cognitive disorders. Discrimination was particularly clear for the dorsal hippocampus, the cerebellar vermis, the dorsal hypothalamus, the caudate nucleus and the lateral part of the frontal cortex. Compared with previous results in rodents, the use of a larger animal model allowed to examine specific brain areas, and generate evidence of the distinct region-specific effects of fetal BPA exposure on the brain metabolome. These modifications occur concomitantly to subtle maternal thyroid function alteration. The functional link between such moderate thyroid changes and fetal brain metabolomic fingerprints remains to be determined as well as the potential implication of other modes of action triggered by BPA such as estrogenic ones. Our results pave the ways for new scientific strategies aiming at linking environmental endocrine disruption and altered neurodevelopment.
Published: 2022

4. Comparative genotoxic potential of 27 polycyclic aromatic hydrocarbons in three human cell lines

Author: Florence Tomasetig, Marc Audebert, Jean Pierre Cravedi, Alexandre R.R. Pery, Vanessa Graillot, C. Tebby, Florence Anna Zeman, 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), Institut National de l'Environnement Industriel et des Risques (INERIS), Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Métabolisme et Xénobiotiques (ToxAlim-MeX), and 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)
Subjects: Modelization, 0301 basic medicine, [SDV]Life Sciences [q-bio], Model parameters, Toxicology, medicine.disease_cause, Cell Line, 03 medical and health sciences, 0302 clinical medicine, In vitro, Cancer risk assessment, polycyclic compounds, medicine, Humans, H2AX, Mutagenicity Tests, Toxic equivalent factor, Chemistry, Low dose, Genetic Variation, General Medicine, Human cell, Polycyclic aromatic hydrocarbons, 3. Good health, 030104 developmental biology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Environmental chemistry, Genotoxicity, 030217 neurology & neurosurgery, DNA Damage, Environmental Monitoring, Mutagens
Abstract: International audience; Polycyclic Aromatic Hydrocarbons (PAHs) form a family of compounds that are generally found in complex mixtures. PAHs can lead to the development of carcinogenesis. The Toxicity Equivalent Factor (TEF) approach has been suggested for estimating the toxicity of PAHs, however, due to the relative weakness of available data, TEF have not been applied for the risk characterization of PAHs as food contaminants in Europe. The determination of new TEFs for a large number of PAHs could overcome some limitations of the current method and improve cancer risk assessment. The present investigation aimed at deriving new TEFs for PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a genotoxicity assay (gamma H2AX) with three human cell lines to analyze the genotoxic properties of 27 selected PAHs after 24 h treatment. For 11 compounds, we did not detect any genotoxic potential. For the remaining 16 PAHs, the concentration-response for genotoxic effect was modelled with the Hill equation; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. We developed for each compound, in each cell line, Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were similar in all cell lines and generally higher than the TEF usually used. These new equivalent factors for PAHs should improve cancer risk assessment.
Published: 2020

5. Despite similar clinical features metabolomics reveals distinct signatures in insulin resistant and progressively obese minipigs

Author: Imene Bousahba, Jérémie David, Florence Castelli, Céline Chollet, Sadia Ouzia, François Fenaille, Didier Rémond, Nathalie Poupin, Sergio Polakof, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), ToxAlim (ToxAlim), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), This study was funded by Agence Nationale de La Recherche (ANR-19-CE14-0026)., and ANR-19-CE14-0026,MelODies,L'utilisation d'une biopsie liquide métabolique pour la détermination de nouveaux biomarqueurs du diabète de type 2 : une approche inter-organe de métabolomique quantitative(2019)
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Physiology, High-fat high-sugar diet, Phenotyping, [SDV]Life Sciences [q-bio], Metabolomics, Type 2 diabetes, General Medicine, Obesity, Biochemistry, Minipigs
Abstract: International audience; Obesity is a major contributor to the silent and progressive development of type 2 diabetes (T2D) whose prevention could be improved if individuals at risk were identified earlier. Our aim is to identify early phenotypes that precede T2D in diet-induced obese minipigs. We fed four groups of minipigs (n = 5–10) either normal-fat or high-fat high-sugar diet during 2, 4, or 6 months. Morphometric features were recorded, and metabolomics and clinical parameters were assessed on fasting plasma samples. Multivariate statistical analysis on 46 morphometrical and clinical parameters allowed to differentiate 4 distinct phenotypes: NFC (control group) and three others (HF2M, HF4M, HF6M) corresponding to the different stages of the obesity progression. Compared to NFC, we observed a rapid progression of body weight and fat mass (4-, 7-, and tenfold) in obese phenotypes. Insulin resistance (IR; 2.5-fold increase of HOMA-IR) and mild dyslipidemia (1.2- and twofold increase in total cholesterol and HDL) were already present in the HF2M and remained stable in HF4M and HF6M. Plasma metabolome revealed subtle changes of 23 metabolites among the obese groups, including a progressive switch in energy metabolism from amino acids to lipids, and a transient increase in de novo lipogenesis and TCA-related metabolites in HF2M. Low anti-oxidative capacities and anti-inflammatory response metabolites were found in the HF4M, and a perturbed hexose metabolism was observed in HF6M. Overall, we show that IR and progressively obese minipigs reveal phenotype-specific metabolomic signatures for which some of the identified metabolites could be considered as potential biomarkers of early progression to TD2.
Published: 2022

6. Modulation of hepatic xenobiotic metabolizing enzymes following chronic low-dose exposure to PFOA in mice

Author: S. Bruel, E. Person, N. Sola-Tapias, Daniel Zalko, Muriel Mercier-Bonin, Hervé Robert, Nicolas J. Cabaton, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), and Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN)
Subjects: 0303 health sciences, Chemistry, [SDV]Life Sciences [q-bio], Low dose, General Medicine, Pharmacology, Toxicology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Xenobiotic metabolizing enzymes, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2021

7. COVID-19: Estimation of the transmission dynamics in Spain using a stochastic simulator and Black-Box optimization techniques

Author: Marcos Matabuena, Carlos García-Meixide, Victor Leboran, Pablo Rodriguez-Mier, Centro Singular de Investigacion en Tecnoloxias da Informacion (CiTIUS), Universidade de Santiago de Compostela [Spain] (USC ), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), This work has received financial support from the Spanish Ministry of Science, Innovation, and Universities under Grant RTI2018- 99646-B-I00, the Consellería de Educación, Universidade e Forma- ción Profesional and the European Regional Development Fund under Grant ED431G-2019/04 ., Universidade de Santiago de Compostela. Centro de Investigación en Tecnoloxías da Información, and Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina
Subjects: Mathematical optimization, Stochastic modelling, Computer science, [SDV]Life Sciences [q-bio], Population, Health Informatics, Stochastic processe, Article, Epidemic models, 03 medical and health sciences, 0302 clinical medicine, Stochastic processes, Seroepidemiologic Studies, Black box, Evolutionary computations, Humans, 030212 general & internal medicine, education, Pandemics, 030304 developmental biology, Retrospective Studies, Flexibility (engineering), 0303 health sciences, education.field_of_study, Stochastic process, SARS-CoV-2, Simulation modeling, COVID-19, Statistical model, 3. Good health, Computer Science Applications, Spain, A priori and a posteriori, Computing science, Software
Abstract: Background and objectives: Epidemiological models of epidemic spread are an essential tool for optimizing decision-making. The current literature is very extensive and covers a wide variety of deterministic and stochastic models. However, with the increase in computing resources, new, more general, and flexible procedures based on simulation models can assess the effectiveness of measures and quantify the current state of the epidemic. This paper illustrates the potential of this approach to build a new dynamic probabilistic model to estimate the prevalence of SARS-CoV-2 infections in different compartments. Methods: We propose a new probabilistic model in which, for the first time in the epidemic literature, parameter learning is carried out using gradient-free stochastic black-box optimization techniques simulating multiple trajectories of the infection dynamics in a general way, solving an inverse problem that is defined employing the daily information from mortality records. Results: After the application of the new proposal in Spain in the first and successive waves, the result of the model confirms the accuracy to estimate the seroprevalence and allows us to know the real dynamics of the pandemic a posteriori to assess the impact of epidemiological measures by the Spanish government and to plan more efficiently the subsequent decisions with the prior knowledge obtained. Conclusions:The model results allow us to estimate the daily patterns of COVID-19 infections in Spain retrospectively and examine the population’s exposure to the virus dynamically in contrast to seroprevalence surveys. Furthermore, given the flexibility of our simulation framework, we can model situations —even using non-parametric distributions between the different compartments in the model— that other models in the existing literature cannot. Our general optimization strategy remains valid in these cases, and we can easily create other non-standard simulation epidemic models that incorporate more complex and dynamic structures This work has received financial support from the Spanish Ministry of Science, Innovation, and Universities under Grant RTI2018-099646-B-I00, the Consellería de Educación, Universidade e Formación Profesional and the European Regional Development Fund under Grant ED431G-2019/04 SI
Published: 2021

8. Uptake, fate, and gut toxicity of perfluorooctanoic acid (PFOA) in vitro

Author: Muriel Mercier-Bonin, Hervé Robert, N. Cabaton, Jean-Nicolas Audinot, C. Stoffels, Mathilde Leveque, Isabelle Fourquaux, E. Person, Vassilia Theodorou, Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), 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), Luxembourg Institute of Science and Technology (LIST), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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)-Hôpital de Rangueil, and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]
Subjects: 0303 health sciences, [SDV]Life Sciences [q-bio], General Medicine, Toxicology, In vitro, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Biochemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, Perfluorooctanoic acid, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2021

9. Transgenerational metabolomic fingerprints in mice ancestrally exposed to the obesogen TBT

Author: Raquel Chamorro-Garcia, Bruce Blumberg, Isabelle Jouanin, Riann Jenay Egusquiza, Bassem M. Shoucri, Marie Tremblay-Franco, Cécile Canlet, Roselyne Gautier, Daniel Zalko, Nathalie Poupin, University of California [Irvine] (UCI), University of California, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), 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), 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 de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), 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)-ToxAlim (ToxAlim), University of California [Irvine] (UC Irvine), University of California (UC), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, and LESUR, Hélène
Subjects: Male, [SDV]Life Sciences [q-bio], Physiology, Disease, Endocrine Disruptors, Metabolic disruptor, Oral and gastrointestinal, mycotoxin, chemistry.chemical_compound, Mice, 0302 clinical medicine, Pregnancy, 2.1 Biological and endogenous factors, Obesogen, GE1-350, Aetiology, General Environmental Science, 0303 health sciences, Liver Disease, Tributyltin, 3. Good health, [SDV] Life Sciences [q-bio], Endocrine disruptor, post-harvest disease, Female, Pediatric Research Initiative, aggressiveness factor, Biology, 03 medical and health sciences, Metabolomics, Insulin resistance, medicine, Metabolome, Animals, Obesity, Penicillium expansum, patulin, Metabolic and endocrine, apples, 030304 developmental biology, Nutrition, Prevention, medicine.disease, Estrogen, Environmental sciences, chemistry, Transgenerational effects, Trialkyltin Compounds, Digestive Diseases, 030217 neurology & neurosurgery, Environmental Sciences
Abstract: Author(s): Chamorro-Garcia, Raquel; Poupin, Nathalie; Tremblay-Franco, Marie; Canlet, Cecile; Egusquiza, Riann; Gautier, Roselyne; Jouanin, Isabelle; Shoucri, Bassem M; Blumberg, Bruce; Zalko, Daniel | Abstract: BackgroundEndocrine disrupting chemicals (EDCs) contribute to the etiology of metabolic disorders such as obesity, insulin resistance and hepatic dysfunction. Concern is growing about the consequences of perinatal EDC exposure on disease predisposition later in life. Metabolomics are promising approaches for studying long-term consequences of early life EDC exposure. These approaches allow for the identification and characterization of biomarkers of direct or ancestral exposures that could be diagnostic for individual susceptibility to disease and help to understand mechanisms through which EDCs act.ObjectivesWe sought to identify metabolomic fingerprints in mice ancestrally exposed to the model obesogen tributyltin (TBT), to assess whether metabolomics could discriminate potential trans-generational susceptibility to obesity and recognize metabolic pathways modulated by ancestral TBT exposure.MethodsWe used non-targeted 1H NMR metabolomic analyses of plasma and liver samples collected from male and female mice ancestrally exposed to TBT in two independent transgenerational experiments in which F3 and F4 males became obese when challenged with increased dietary fat.ResultsMetabolomics confirmed transgenerational obesogenic effects of environmentally relevant doses of TBT in F3 and F4 males, in two independent studies. Although females never became obese, their specific metabolomic fingerprint evidenced distinct transgenerational effects of TBT in female mice consistent with impaired capacity for liver biotransformation.DiscussionThis study is the first application of metabolomics to unveil the transgenerational effects of EDC exposure. Very early, significant changes in the plasma metabolome were observed in animals ancestrally exposed to TBT. These changes preceded the onset of obesogenic effects elicited by increased dietary fat in the TBT groups, and which ultimately resulted in significant changes in the liver metabolome. Development of metabolomic fingerprints could facilitate the identification of individuals carrying the signature of ancestral obesogen exposure that might increase their susceptibility to other risk factor such as increased dietary fat.
Published: 2021

10. Atopic dermatitis or eczema? Consequences of ambiguity in disease name for biomedical literature mining

Author: Sarah Filippi, Marina Evangelou, Yoann Pitarch, Clément Frainay, Adnan Custovic, Imperial College London, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Recherche d’Information et Synthèse d’Information (IRIT-IRIS), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, and UK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission
Subjects: Medical terminology, GENES, Allergy, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Immunology, Decision tree, Eczema, text mining, computer.software_genre, Terminology, TEXT, Dermatitis, Atopic, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, Terminology as Topic, medical terminology, medicine, Immunology and Allergy, Data Mining, Humans, information retrieval, REVISED NOMENCLATURE, 030304 developmental biology, media_common, 0303 health sciences, Science & Technology, atopic dermatitis, business.industry, Decision tree learning, Subject (documents), Atopic dermatitis, Ambiguity, medicine.disease, 3. Good health, Systematic review, 030228 respiratory system, 1107 Immunology, 1111 Nutrition and Dietetics, Artificial intelligence, business, Psychology, computer, Life Sciences & Biomedicine, Natural language processing
Abstract: International audience; Background: Biomedical research increasingly relies on computational approaches to extract relevant information from large corpora of publications.Objective: To investigate the consequence of the ambiguity between the use of terms "Eczema" and "Atopic Dermatitis" (AD) from the Information Retrieval perspective, and its impact on meta-analyses, systematic reviews and text mining.Methods: Articles were retrieved by querying the PubMed using terms 'eczema' (D003876) and "dermatitis, atopic" (D004485). We used machine learning to investigate the differences between the contexts in which each term is used. We used a decision tree approach and trained model to predict if an article would be indexed with eczema or AD tags. We used text-mining tools to extract biological entities associated with eczema and AD, and investigated the discrepancy regarding the retrieval of key findings according to the terminology used.Results: Atopic dermatitis query yielded more articles related to veterinary science, biochemistry, cellular and molecular biology; the eczema query linked to public health, infectious disease and respiratory system. Medical Subject Headings terms associated with "AD" or "Eczema" differed, with an agreement between the top 40 lists of 52%. The presence of terms related to cellular mechanisms, especially allergies and inflammation, characterized AD literature. The metabolites mentioned more frequently than expected in articles with AD tag differed from those indexed with eczema. Fewer enriched genes were retrieved when using eczema compared to AD query.Conclusions and clinical relevance: There is a considerable discrepancy when using text mining to extract bio-entities related to eczema or AD. Our results suggest that any systematic approach (particularly when looking for metabolites or genes related to the condition) should be performed using both terms jointly. We propose to use decision tree learning as a tool to spot and characterize ambiguity, and provide the source code for disambiguation at https://github.com/cfrainay/ResearchCodeBase.
Published: 2021

11. Osteogenic Response of Human Mesenchymal Stem Cells Analysed Using Combined Intracellular and Extracellular Metabolomic Monitoring

Author: Fabien Jourdan, Dong-Hyun Kim, Amal Surrati, Sergey Evseev, Virginie Sottile, University of Nottingham, UK (UON), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), and University of Pavia
Subjects: Physiology, Metabolite, Cellular differentiation, Metabolomics profiling, [SDV]Life Sciences [q-bio], QD415-436, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Metabolomics, Osteogenesis, medicine, Extracellular, Humans, QP1-981, Progenitor cell, 030304 developmental biology, Cell Line, Transformed, 0303 health sciences, Chemistry, 030302 biochemistry & molecular biology, Mesenchymal stem cell, Cell Differentiation, Cell biology, LC-MS, medicine.anatomical_structure, Differentiation, Metabolome, Mesenchymal stem cells, Bone marrow, Stem cell
Abstract: International audience; Background/Aims: The skeleton is a metabolically active organ undergoing continuous remodelling initiated by mesenchymal progenitors present in bone and bone marrow. Under certain pathological conditions this remodelling balance shifts towards increased resorption resulting in weaker bone microarchitecture, and there is consequently a therapeutic need to identify pathways that could inversely enhance bone formation from stem cells. Metabolomics approaches recently applied to stem cell characterisation could help identify new biochemical markers involved in osteogenic differentiation. Methods: Combined intra- and extracellular metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS) on human mesenchymal stem cells (MSCs) undergoing osteogenic differentiation in vitro. Using a combination of univariate and multivariate analyses, changes in metabolite and nutrient concentration were monitored in cultures under osteogenic treatment over 10 days. Results: A subset of differentially detected compounds was identified in differentiating cells, suggesting a direct link to metabolic processes involved in osteogenic response. Conclusion: These results highlight new metabolite candidates as potential biomarkers to monitor stem cell differentiation towards the bone lineage.
Published: 2021

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

Author: Frédéric Lasserre, Sharon Barretto, Maïwenn Olier, Laurence Gamet-Payrastre, Claire Naylies, Hervé Guillou, Sandrine Bruel, Laurence Guzylack, Nicolas Loiseau, Céline Lukowicz, Elodie Person, Colette Bétoulières, Marion Régnier, Laila Mselli-Lakhal, Vassilia Theodorou, Walter Wahli, Anne Fougerat, Yannick Lippi, Arnaud Polizzi, Sarra Smati, Sandrine Ellero-Simatos, Daniel Zalko, Marine Huillet, 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), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), 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), Transcriptomic impact of Xenobiotics (E23 TRiX), 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)-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), Métabolisme et Xénobiotiques (ToxAlim-MeX), Plateforme Ezop (Ezop), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], 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 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), Nanyang Technological University (NTU), and Lee Kong Chian School of Medicine (LKCMedicine)
Subjects: Male, Microbiology (medical), medicine.medical_specialty, [SDV]Life Sciences [q-bio], Gut microbiota, Gut flora, Microbiology, digestive system, Xenobiotics, Transcriptome, Microbial ecology, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, NR1I2, Internal medicine, medicine, Animals, Female, Gastrointestinal Microbiome/genetics, Lipids, Liver, Mice, Inbred C57BL, Pregnane X Receptor/genetics, Fatty acid metabolism, Pregnane X receptor, Transcriptomics, Xenobiotic metabolism, Gut Microbiota, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, biology, Effector, Research, QR100-130, Fatty acid, Biological sciences [Science], biology.organism_classification, digestive system diseases, Gastrointestinal Microbiome, 3. Good health, Endocrinology, chemistry, 030220 oncology & carcinogenesis, Xenobiotic, Drug metabolism
Abstract: Background The gut microbiota–intestine–liver relationship is emerging as an important factor in multiple hepatic pathologies, but the hepatic sensors and effectors of microbial signals are not well defined. Results By comparing publicly available liver transcriptomics data from conventional vs. germ-free mice, we identified pregnane X receptor (PXR, NR1I2) transcriptional activity as strongly affected by the absence of gut microbes. Microbiota depletion using antibiotics in Pxr+/+vs Pxr-/- C57BL/6J littermate mice followed by hepatic transcriptomics revealed that most microbiota-sensitive genes were PXR-dependent in the liver in males, but not in females. Pathway enrichment analysis suggested that microbiota–PXR interaction controlled fatty acid and xenobiotic metabolism. We confirmed that antibiotic treatment reduced liver triglyceride content and hampered xenobiotic metabolism in the liver from Pxr+/+ but not Pxr-/- male mice. Conclusions These findings identify PXR as a hepatic effector of microbiota-derived signals that regulate the host’s sexually dimorphic lipid and xenobiotic metabolisms in the liver. Thus, our results reveal a potential new mechanism for unexpected drug–drug or food–drug interactions.
Published: 2021

13. Mitochondrial metabolism supports resistance to IDH mutant inhibitors in acute myeloid leukemia

Author: Lara Gales, Camille Montersino, Marc Conti, Pierre Bories, Courtney D. DiNardo, Brandon Nicolay, Fabien Jourdan, Nicolas Broin, Mohsen Hosseini, Guillaume Cognet, Yves Gibon, Marie Sabatier, Tony Kaoma, Marina Konopleva, Lucille Stuani, Mathilde Gotanègre, Christian Recher, Laurent Fernando, Vera Pancaldi, Nathalie Poupin, Estelle Saland, Jean-Emmanuel Sarry, Joseph R. Marszalek, Andrei Turtoi, Thomas Farge, Feng Wang, Yves Collette, Laurent Le Cam, Madi Y. Cissé, Cédric Cassan, Alexis Hucteau, Claudie Bosc, Natalia Baran, Sebastien Ronseaux, Aliki Zavoriti, François Fenaille, Florence Castelli, Laetitia K. Linares, Evgenia Turtoi, Emeline Chu-Van, Martin Carroll, Pierre-Luc Mouchel, Mary A. Selak, Guillaume Cazals, Emeline Boet, Rémy Castellano, Floriant Bellvert, Norbert Vey, Clément Larrue, Koichi Takahashi, Ambrine Sahal, Sylvain Loric, Jean-Charles Portais, Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire d'Etude du Métabolisme des Médicaments (LEMM), 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)-Médicaments et Technologies pour la Santé (MTS), 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), Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Institut National de la Santé et de la Recherche Médicale (INSERM), Luxembourg Institute of Health (LIH), Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Pennsylvania, Université de Montpellier (UM), Réseau régional de cancérologie Onco-Occitanie, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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)-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), Agios Pharmaceuticals, ANR-11-PHUC-0001,CAPTOR,Cancer et Pharmacologie : Projet de Toulouse-Oncopole et de sa Région(2011), ANR-11-LABX-0068,TOUCAN,Analyse intégrée de la résistance dans les cancers hématologiques(2011), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Toulouse [Toulouse]-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), University of Pennsylvania [Philadelphia], Laboratoire de Mesures Physiques, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-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 Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), collette, yves, Pôle hospitalier Universitaire Cancer (PHUC) - Cancer et Pharmacologie : Projet de Toulouse-Oncopole et de sa Région - - CAPTOR2011 - ANR-11-PHUC-0001 - PHUC - VALID, Analyse intégrée de la résistance dans les cancers hématologiques - - TOUCAN2011 - ANR-11-LABX-0068 - LABX - VALID, and Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID
Subjects: Pyridines, [SDV]Life Sciences [q-bio], Mutant, Aminopyridines, Mice, SCID, Mitochondrion, medicine.disease_cause, Oxidative Phosphorylation, Epigenesis, Genetic, 0302 clinical medicine, Piperidines, Mice, Inbred NOD, hemic and lymphatic diseases, Immunology and Allergy, Enzyme Inhibitors, Mice, Knockout, 0303 health sciences, Mutation, Oxadiazoles, Chemistry, Triazines, Myeloid leukemia, Isocitrate Dehydrogenase, 3. Good health, Mitochondria, [SDV] Life Sciences [q-bio], Isoenzymes, Leukemia, Leukemia, Myeloid, 030220 oncology & carcinogenesis, Doxycycline, Acute Disease, Immunology, Glycine, HL-60 Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, Humans, Epigenetics, Protein kinase B, 030304 developmental biology, medicine.disease, Xenograft Model Antitumor Assays, Leukemia & Lymphoma, Metabolism, Drug Resistance, Neoplasm, Cancer cell, Cancer research
Abstract: Stuani et al. demonstrate that IDH mutant AML cells display an enhanced mitochondrial phenotype, which is not reversed by IDH mutant inhibitors. This study provides a scientific rationale for combinatory mitochondrial-targeted therapies to treat IDH mutant AML patients, especially those unresponsive to or relapsing from IDH mutant inhibitors., Mutations in IDH induce epigenetic and transcriptional reprogramming, differentiation bias, and susceptibility to mitochondrial inhibitors in cancer cells. Here, we first show that cell lines, PDXs, and patients with acute myeloid leukemia (AML) harboring an IDH mutation displayed an enhanced mitochondrial oxidative metabolism. Along with an increase in TCA cycle intermediates, this AML-specific metabolic behavior mechanistically occurred through the increase in electron transport chain complex I activity, mitochondrial respiration, and methylation-driven CEBPα-induced fatty acid β-oxidation of IDH1 mutant cells. While IDH1 mutant inhibitor reduced 2-HG oncometabolite and CEBPα methylation, it failed to reverse FAO and OxPHOS. These mitochondrial activities were maintained through the inhibition of Akt and enhanced activation of peroxisome proliferator-activated receptor-γ coactivator-1 PGC1α upon IDH1 mutant inhibitor. Accordingly, OxPHOS inhibitors improved anti-AML efficacy of IDH mutant inhibitors in vivo. This work provides a scientific rationale for combinatory mitochondrial-targeted therapies to treat IDH mutant AML patients, especially those unresponsive to or relapsing from IDH mutant inhibitors., Graphical Abstract
Published: 2021

14. Safety assessment of cosmetics by read across applied to metabolomics data of in vitro skin and liver models

Author: Sandrine Bessou-Touya, Marie Tremblay-Franco, Yves Brunel, Hélène Duplan, Cécile Canlet, Emilien L. Jamin, Daniel Zalko, Carine Jacques, Jean-François Martin, Laurent Debrauwer, Pierre-Jacques Ferret, Isabelle Jouanin, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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)-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)-ToxAlim (ToxAlim), 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)-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), ToxAlim (ToxAlim), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), 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), 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 des Sciences Appliquées - Toulouse (INSA Toulouse)
Subjects: Swine, Health, Toxicology and Mutagenesis, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Skin mode, Cosmetics, Pharmacology, Toxicology, Cell Line, 03 medical and health sciences, Animal data, 0302 clinical medicine, Metabolomics, In vivo, Toxicity Tests, Metabolome, Animals, Humans, Cells, Cultured, 030304 developmental biology, media_common, Skin, Skin metabolism, 0303 health sciences, Chemistry, In vitro toxicology, Lipid metabolism, General Medicine, 3. Good health, Liver, Consumer Product Safety, 030220 oncology & carcinogenesis, Toxicity, Read-across, Female, Decanoic Acids
Abstract: International audience; As a result of the cosmetics testing ban, safety evaluations of cosmetics ingredients must now be conducted using animal-free methods. A common approach is read across, which is mainly based on structural similarities but can also be conducted using biological endpoints. Here, metabolomics was used to assess biological effects to enable a read across between a candidate cosmetic ingredient, DIV665, only studied using in vitro assays, and a structurally similar reference compound, PA102, previously investigated using traditional in vivo toxicity methods. The (1) cutaneous distribution after topical application, (2) skin metabolism, (3) liver metabolism and (4) effect on the intracellular metabolomic profiles of in vitro skin and hepatic models, SkinEthic®RHE model and HepaRG® cells were investigated. The compounds exhibited similar skin penetration and skin and liver metabolism, with small differences attributed to their physicochemical properties. The effects of both compounds on the metabolome of RHE and HepaRG® cells were similarly small, both in terms of the metabolites modulated and the magnitude of changes. The patterns of metabolome changes did not fit with any known signature relating to a mode of action known to be linked to liver toxicity e.g. modification of the Krebs cycle, urea synthesis and lipid metabolism, were more reflective of transient adaptive responses. Overall, these studies indicate that PA102 is biologically similar to DIV665, allowing read across of safety endpoints, such as in vivo sub-chronic (but not reproduction toxicity) studies, for the former to be applied to DIV665. Based on this, in the absence of animal data (which is prohibited for new chemicals), it could be concluded that DIV665 applied according to the consumer topical use scenario, is similar to PA102, and is predicted to exhibit low local skin and systemic toxicity
Published: 2021

15. An Integrated Analysis of miRNA and Gene Expression Changes in Response to an Obesogenic Diet to Explore the Impact of Transgenerational Supplementation with Omega 3 Fatty Acids

Author: Béatrice Morio, Nathalie Poupin, Alexandre Pinel, Karla Fabiola Corral-Jara, Sarah de Saint Vincent, Tao Ye, Frédéric Capel, Jean Paul Rigaudière, Laura Cantini, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), Avril Lesieur European Union (EU), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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 National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LESUR, Hélène, and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: 0301 basic medicine, Male, obesity, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Gene Expression, Type 2 diabetes, Bioinformatics, Mice, 0302 clinical medicine, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, Metabolic Syndrome, Nutrition and Dietetics, microRNA, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Eicosapentaenoic acid, [SDV] Life Sciences [q-bio], lcsh:Nutrition. Foods and food supply, Polyunsaturated fatty acid, lcsh:TX341-641, Biology, Diet, High-Fat, liver, Article, 03 medical and health sciences, omega 3 fatty acids, Insulin resistance, Fatty Acids, Omega-3, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Insulin, medicine.disease, IRS2, Mice, Inbred C57BL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Disease Models, Animal, MicroRNAs, 030104 developmental biology, chemistry, Dietary Supplements, Metabolic syndrome, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, transcriptome, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: Insulin resistance decreases the ability of insulin to inhibit hepatic gluconeogenesis, a key step in the development of metabolic syndrome. Metabolic alterations, fat accumulation, and fibrosis in the liver are closely related and contribute to the progression of comorbidities, such as hypertension, type 2 diabetes, or cancer. Omega 3 (n-3) polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), were identified as potent positive regulators of insulin sensitivity in vitro and in animal models. In the current study, we explored the effects of a transgenerational supplementation with EPA in mice exposed to an obesogenic diet on the regulation of microRNAs (miRNAs) and gene expression in the liver using high-throughput techniques. We implemented a comprehensive molecular systems biology approach, combining statistical tools, such as MicroRNA Master Regulator Analysis pipeline and Boolean modeling to integrate these biochemical processes. We demonstrated that EPA mediated molecular adaptations, leading to the inhibition of miR-34a-5p, a negative regulator of Irs2 as a master regulatory event leading to the inhibition of gluconeogenesis by insulin during the fasting&ndash, feeding transition. Omics data integration provided greater biological insight and a better understanding of the relationships between biological variables. Such an approach may be useful for deriving innovative data-driven hypotheses and for the discovery of molecular&ndash, biochemical mechanistic links.
Published: 2020

16. An Optimized Dual Extraction Method for the Simultaneous and Accurate Analysis of Polar Metabolites and Lipids Carried out on Single Biological Samples

Author: Villaret-Cazadamont, Joran, Poupin, Nathalie, Tournadre, Anthony, Batut, Aurélie, Gales, Lara, Zalko, Daniel, Cabaton, Nicolas J., Bellvert, Floriant, Bertrand-Michel, Justine, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Métabolomique et Fluxomique (MetaToul) (TBI-MetaToul), 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), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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, 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), Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French National Research Program for Environmental and Occupational Health of Anses 2018/1/172, INRAE Human Nutrition division, Région Occitanie, LESUR, Hélène, MetaToul FluxoMet (TBI-MetaToul), 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)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-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)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-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)-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)-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 (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-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)-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)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-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)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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, 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 Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: hepatotoxicity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, sample preparation, [SDV]Life Sciences [q-bio], lcsh:QR1-502, metabolomics, lcsh:Microbiology, Article, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, multi-omics analysis, [SDV.TOX]Life Sciences [q-bio]/Toxicology, lipidomics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, dual extraction
Abstract: International audience; The functional understanding of metabolic changes requires both a significant investigation into metabolic pathways, as enabled by global metabolomics and lipidomics approaches, and the comprehensive and accurate exploration of specific key pathways. To answer this pivotal challenge, we propose an optimized approach, which combines an efficient sample preparation, aiming to reduce the variability, with a biphasic extraction method, where both the aqueous and organic phases of the same sample are used for mass spectrometry analyses. We demonstrated that this double extraction protocol allows working with one single sample without decreasing the metabolome and lipidome coverage. It enables the targeted analysis of 40 polar metabolites and 82 lipids, together with the absolute quantification of 32 polar metabolites, providing comprehensive coverage and quantitative measurement of the metabolites involved in central carbon energy pathways. With this method, we evidenced modulations of several lipids, amino acids, and energy metabolites in HepaRG cells exposed to fenofibrate, a model hepatic toxicant, and metabolic modulator. This new protocol is particularly relevant for experiments involving limited amounts of biological material and for functional metabolic explorations and is thus of particular interest for studies aiming to decipher the effects and modes of action of metabolic disrupting compounds.
Published: 2020

17. Postprandial NMR-Based Metabolic Exchanges Reflect Impaired Phenotypic Flexibility across Splanchnic Organs in the Obese Yucatan Mini-Pig

Author: Isabelle Savary-Auzeloux, Cécile Canlet, Nathalie Poupin, Dominique Dardevet, Marie Tremblay-Franco, Aurélien Amiel, Fabien Jourdan, Sergio Polakof, Laurent Debrauwer, Didier Rémond, Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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)-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)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul FluxoMet (TBI-MetaToul), 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)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-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)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INRAE AlimH department funding French Infrastructure for Metabolomics and Fluxomics MetaboHUB-ANR-11-INBS-0010, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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-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 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), 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-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-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), Métabolomique et Fluxomique (MetaToul) (TBI-MetaToul), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and 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)
Subjects: 0301 basic medicine, Blood Glucose, Magnetic Resonance Spectroscopy, Swine, high fat-high sucrose diet, [SDV]Life Sciences [q-bio], postprandial, mini-pigs, chemistry.chemical_compound, 0302 clinical medicine, Dietary Sucrose, energy metabolism, Glucose homeostasis, Homeostasis, Intestinal Mucosa, Nutrition and Dietetics, Glycogen, Postprandial Period, metabolomics, Postprandial, Swine, Miniature, Animal Nutritional Physiological Phenomena, Female, Splanchnic, lcsh:Nutrition. Foods and food supply, arteriovenous differences, medicine.medical_specialty, 030209 endocrinology & metabolism, lcsh:TX341-641, Biology, Diet, High-Fat, liver, Article, 03 medical and health sciences, Metabolomics, Insulin resistance, Internal medicine, medicine, Metabolome, Animals, Obesity, intestine, phenotypic flexibility, medicine.disease, 030104 developmental biology, Endocrinology, chemistry, Insulin Resistance, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: The postprandial period represents one of the most challenging phenomena in whole-body metabolism, and it can be used as a unique window to evaluate the phenotypic flexibility of an individual in response to a given meal, which can be done by measuring the resilience of the metabolome. However, this exploration of the metabolism has never been applied to the arteriovenous (AV) exploration of organs metabolism. Here, we applied an AV metabolomics strategy to evaluate the postprandial flexibility across the liver and the intestine of mini-pigs subjected to a high fat&ndash, high sucrose (HFHS) diet for 2 months. We identified for the first time a postprandial signature associated to the insulin resistance and obesity outcomes, and we showed that the splanchnic postprandial metabolome was considerably affected by the meal and the obesity condition. Most of the changes induced by obesity were observed in the exchanges across the liver, where the metabolism was reorganized to maintain whole body glucose homeostasis by routing glucose formed de novo from a large variety of substrates into glycogen. Furthermore, metabolites related to lipid handling and energy metabolism showed a blunted postprandial response in the obese animals across organs. Finally, some of our results reflect a loss of flexibility in response to the HFHS meal challenge in unsuspected metabolic pathways that must be further explored as potential new events involved in early obesity and the onset of insulin resistance.
Published: 2020

18. The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds

Author: Legler, Juliette, Zalko, Daniel, Jourdan, Fabien, Jacobs, Miriam, Fromenty, Bernard, Balaguer, Patrick, Bourguet, William, Munic Kos, Vesna, Nadal, Angel, Beausoleil, Claire, Cristobal, Susana, Remy, Sylvie, Ermler, Sibylle, Margiotta-Casaluci, Luigi, Griffin, Julian L., Blumberg, Bruce, Chesné, Christophe, Hoffmann, Sebastian, Andersson, Patrik L., Kamstra, Jorke H., Dep Population Health Sciences, IRAS OH Toxicology, dIRAS RA-1, Utrecht University [Utrecht], Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Centre for Radiation, Chemical and Environmental Hazards, Public Health England [London], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institutet [Stockholm], Universidad Miguel Hernández [Elche] (UMH), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Linköping University (LIU), Flemish Institute for Technological Research (VITO), Department of Life Sciences, College of Health and Life Sciences, Brunel University London [Uxbridge], Imperial College London, University of California [Irvine] (UCI), University of California, Biopredic International [Saint-Grégoire], Seh consulting, Umeå University, Department of Chemistry, European Union's Horizon 2020 research and innovation program under grant agreement GOLIATH No. 825489., Université de Rennes (UR)-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 de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of California (UC), Umeå University, European Project: 825489,H2020,GOLIATH(2019), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 825489, Horizon 2020, inrae, LESUR, Hélène, Beating Goliath: Generation Of NoveL, Integrated and Internationally Harmonised Approaches for Testing Metabolism Disrupting Compounds - GOLIATH - - H20202019-01-19 - 2023-12-31 - 825489 - VALID, Dep Population Health Sciences, IRAS OH Toxicology, and dIRAS RA-1
Subjects: 0301 basic medicine, obesity, [SDV]Life Sciences [q-bio], risk assessment, 010501 environmental sciences, Endocrine Disruptors, MESH: Risk Assessment, 01 natural sciences, lcsh:Chemistry, Adverse Outcome Pathway, Adipocytes, chemicals, MESH: Obesity, lcsh:QH301-705.5, MESH: Fatty Liver, Spectroscopy, diabetes, Biochemistry and Molecular Biology, General Medicine, Integrated approach, Farmakologi och toxikologi, 3. Good health, Computer Science Applications, MESH: Endocrine Disruptors, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, Risk analysis (engineering), [SDV.TOX]Life Sciences [q-bio]/Toxicology, Metabolic Networks and Pathways, Project Report, MESH: Diabetes Mellitus, endocrine, 0699 Other Biological Sciences, Pharmacology and Toxicology, Catalysis, Inorganic Chemistry, 03 medical and health sciences, 0399 Other Chemical Sciences, Diabetes Mellitus, Genetics, Humans, Physical and Theoretical Chemistry, Molecular Biology, MESH: Adipocytes, Metabolic and endocrine, 0105 earth and related environmental sciences, Metabolic health, Nutrition, 0604 Genetics, Chemical Physics, Organic Chemistry, Estrogen, Fatty Liver, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, 13. Climate action, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Business, Other Biological Sciences, Other Chemical Sciences, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biokemi och molekylärbiologi
Abstract: International audience; The purpose of this project report is to introduce the European "GOLIATH" project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as "metabolism Int. Int. J. Mol. Sci. 2020, 21, 3480 2 of 18 disrupting compounds" (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world's first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption-hepatocytes, pancreatic endocrine cells, myocytes and adipocytes-and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.
Published: 2020

19. The trouble with endocrine disruptors

Author: Daniel Zalko, Catherine Viguié, Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), 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), and Métabolisme et Xénobiotiques (ToxAlim-MeX)
Subjects: 0303 health sciences, business.industry, [SDV]Life Sciences [q-bio], MEDLINE, 030209 endocrinology & metabolism, Environmental Exposure, Complex Mixtures, Endocrine Disruptors, Wastewater, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Bioinformatics, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Toxicity Tests, Animals, Humans, Medicine, Endocrine system, Environmental Pollutants, business, Molecular Biology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology
Published: 2020

20. Synergic toxic effects of food contaminant mixtures in human cells

Author: Imourana Alassane-Kpembi, Marc Audebert, Pascal Sanders, Daniel Zalko, Valérie Fessard, Benjamin Kopp, Ludovic Le Hégarat, 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), Laboratoire de Fougères - ANSES, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Métabolisme et Xénobiotiques (ToxAlim-MeX), and 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)
Subjects: DNA damage, DNA repair, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, DNA Repair Inhibition, chemistry.chemical_element, 010501 environmental sciences, Toxicology, medicine.disease_cause, 01 natural sciences, 03 medical and health sciences, Genetics, medicine, Cytotoxicity, Genetics (clinical), 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, Cadmium, Mutagenesis, 3. Good health, chemistry, Biochemistry, 13. Climate action, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Environmental toxicology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genotoxicity
Abstract: Humans are exposed to multiple exogenous substances, notably through food consumption. Many of these compounds are suspected to impact human health, and their combination could exacerbate their harmful effects. We previously observed in human cells that, among the six most prevalent food contaminant complex mixtures identified in the French diet, synergistic interactions between component appeared in two mixtures compared with the response with the chemicals alone. In the present study, we demonstrated in human cells that these properties are driven only by two heavy metals in each mixture: tellurium (Te) with cadmium (Cd) and Cd with inorganic arsenic (As), respectively. It appeared that the predicted effects for these binary mixtures using the mathematical model of Chou and Talalay confirmed synergism between these heavy metals. Based on different cell biology experiments (cytotoxicity, genotoxicity, mutagenesis and DNA repair inhibition experiments), a detailed mechanistic analysis of these two mixtures suggests that concomitant induction of oxidative DNA damage and decrease of their repair capacity contribute to the synergistic toxic effect of these chemical mixtures. Overall, these results may have broad implications for the fields of environmental toxicology and chemical mixture risk assessment.
Published: 2020

21. Important Considerations for Sample Collection in Metabolomics Studies with a Special Focus on Applications to Liver Functions

Author: Lorraine Smith, Cécile Canlet, Hervé Guillou, Nicolas J. Cabaton, Sandrine P. Claus, Joran Villaret-Cazadamont, Sandrine Ellero-Simatos, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), 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), Métabolisme et Xénobiotiques (ToxAlim-MeX), LNC Therapeut, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), 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-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), 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, Computer science, Endocrinology, Diabetes and Metabolism, Operating procedures, [SDV]Life Sciences [q-bio], High variability, lcsh:QR1-502, Review, Computational biology, 01 natural sciences, Biochemistry, lcsh:Microbiology, 03 medical and health sciences, Metabolomics, blood, Molecular Biology, standard operating procedures, 010401 analytical chemistry, Nutritional status, tissue, metabolomics, urine, 0104 chemical sciences, 3. Good health, 030104 developmental biology, Liver metabolism, feces, liver function, [SDV.TOX]Life Sciences [q-bio]/Toxicology, cells, Sample collection, Liver function, Liver functions, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Metabolomics has found numerous applications in the study of liver metabolism in health and disease. Metabolomics studies can be conducted in a variety of biological matrices ranging from easily accessible biofluids such as urine, blood or feces, to organs, tissues or even cells. Sample collection and storage are critical steps for which standard operating procedures must be followed. Inappropriate sample collection or storage can indeed result in high variability, interferences with instrumentation or degradation of metabolites. In this review, we will first highlight important general factors that should be considered when planning sample collection in the study design of metabolomic studies, such as nutritional status and circadian rhythm. Then, we will discuss in more detail the specific procedures that have been described for optimal pre-analytical handling of the most commonly used matrices (urine, blood, feces, tissues and cells).
Published: 2020

22. Evaluation of the genotoxic potential of apoptosis inducers with the γH2AX assay in human cells

Author: Daniel Zalko, Marc Audebert, Laure Khoury, 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), Métabolisme et Xénobiotiques (ToxAlim-MeX), and 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)
Subjects: 0301 basic medicine, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Blotting, Western, Gene Expression, Apoptosis, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Histones, 03 medical and health sciences, Clastogen, In vivo, Cell Line, Tumor, Genetics, medicine, Biomarkers, Tumor, Humans, H2AX, Phosphorylation, Micronuclei, Chromosome-Defective, 0105 earth and related environmental sciences, Micronucleus Tests, Chemistry, Mutagenicity Tests, Epithelial Cells, Hep G2 Cells, In vitro, 3. Good health, Biomarker, 030104 developmental biology, Micronucleus, Proto-Oncogene Proteins c-bcl-2, Cell culture, Cancer research, Cell lines, Genotoxicity, Mutagens
Abstract: Human risk assessment of genotoxic chemicals is an important area of research. However, the specificity of in vitro mammalian genotoxicity assays is sometime low, as they yield to misleading positive results that are not observe in in vivo studies. Apoptosis can be a confounding factor in the interpretation of the results. Recently, a new strategy for genotoxicity screening, based on the combined analysis of phosphorylated histones H2AX (gamma H2AX) and H3 (pH3), was proposed to discriminate efficiently aneugenic from clastogenic compounds. However, gamma H2AX biomarker could also be induce by apoptosis. The aim of the present study was to investigate the specificity of this genotoxic biomarker. For this purpose, we analyzed 26 compounds inducing apoptosis by different mechanism of action, with the gamma H2AX assay in three human cell lines after 24 h treatment. Most of the tested chemicals were negative in the assay, whatever the cell line tested. The few compounds that generated positive data have also been report positive in other genotoxicity assays. The data presented here demonstrate that the gamma H2AX assay is not vulnerable to the generation of misleading positive results by apoptosis inducers. Currently, no formal guidelines have been approve for the gamma H2AX assay for regular genotoxicity studies, but we suggest that this biomarker could be used as a new standard genotoxicity assay.
Published: 2019

23. Pathway analysis in metabolomics: Recommendations for the use of over-representation analysis

Author: Pablo Rodriguez-Mier, Cecilia Wieder, Fabien Jourdan, Nathalie Poupin, Rachel P. J. Lai, Timothy M. D. Ebbels, Clément Frainay, Florence Vinson, Jacob G. Bundy, Juliette Cooke, Imperial College London, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Métabolomique et Fluxomique (MetaToul) (TBI-MetaToul), 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), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This research was funded in whole, or in part, by the Wellcome Trust [222837/Z/21/Z]. CW is supported by a Wellcome Trust PhD Studentship [222837/Z/21/Z]. RPJL receives support from the UK Medical Research Council (MR/R008922/1). JC is supported by a state-funded PhD contract (MESRI (Minister of Higher Education, Research and Innovation)). FJ is supported by the French Ministry of Research and National Research Agency as part of the French MetaboHUB, the national metabolomics and fluxomics infrastructure (Grant ANR-INBS-0010), and MetClassNet project (ANR-19-CE45-0021 and DFG: 431572533), ANR-19-CE45-0021,MetClassNet,Nouvelles approches pour combiner les réseaux métaboliques et la métabolomique non ciblée(2019), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul FluxoMet (TBI-MetaToul), 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)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-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)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LESUR, Hélène, Nouvelles approches pour combiner les réseaux métaboliques et la métabolomique non ciblée - - MetClassNet2019 - ANR-19-CE45-0021 - AAPG2019 - VALID, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, 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)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-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)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Physiology, Computer science, [SDV]Life Sciences [q-bio], Datasets as Topic, Biochemistry, 0302 clinical medicine, Metabolites, Biology (General), Protein Metabolism, 0303 health sciences, Ecology, Genomics, Pathway analysis, 3. Good health, [SDV] Life Sciences [q-bio], Chemistry, Identification (information), Physiological Parameters, Computational Theory and Mathematics, 030220 oncology & carcinogenesis, Modeling and Simulation, Physical Sciences, Metabolic Pathways, Selection method, Transcriptome Analysis, Metabolic Networks and Pathways, Network Analysis, Research Article, Chemical Elements, Computer and Information Sciences, QH301-705.5, MEDLINE, Computational biology, Over representation, Metabolic Networks, 03 medical and health sciences, Cellular and Molecular Neuroscience, Metabolomics, Genetics, KEGG, Set (psychology), Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Body Weight, Computational Biology, Reproducibility of Results, Biology and Life Sciences, Genome Analysis, Metabolism
Abstract: Over-representation analysis (ORA) is one of the commonest pathway analysis approaches used for the functional interpretation of metabolomics datasets. Despite the widespread use of ORA in metabolomics, the community lacks guidelines detailing its best-practice use. Many factors have a pronounced impact on the results, but to date their effects have received little systematic attention. Using five publicly available datasets, we demonstrated that changes in parameters such as the background set, differential metabolite selection methods, and pathway database used can result in profoundly different ORA results. The use of a non-assay-specific background set, for example, resulted in large numbers of false-positive pathways. Pathway database choice, evaluated using three of the most popular metabolic pathway databases (KEGG, Reactome, and BioCyc), led to vastly different results in both the number and function of significantly enriched pathways. Factors that are specific to metabolomics data, such as the reliability of compound identification and the chemical bias of different analytical platforms also impacted ORA results. Simulated metabolite misidentification rates as low as 4% resulted in both gain of false-positive pathways and loss of truly significant pathways across all datasets. Our results have several practical implications for ORA users, as well as those using alternative pathway analysis methods. We offer a set of recommendations for the use of ORA in metabolomics, alongside a set of minimal reporting guidelines, as a first step towards the standardisation of pathway analysis in metabolomics., Author summary Metabolomics is a rapidly growing field of study involving the profiling of small molecules within an organism. It allows researchers to understand the effects of biological status (such as health or disease) on cellular biochemistry, and has wide-ranging applications, from biomarker discovery and personalised medicine in healthcare to crop protection and food security in agriculture. Pathway analysis helps to understand which biological pathways, representing collections of molecules performing a particular function, may be involved in response to a disease phenotype, or drug treatment, for example. Over-representation analysis (ORA) is perhaps the most common pathway analysis method used in the metabolomics community. However, ORA can give drastically different results depending on the input data and parameters used. Here, we have established the effects of these factors on ORA results using computational modifications applied to five real-world datasets. Based on our results, we offer the research community a set of best-practice recommendations applicable not only to ORA but also to other pathway analysis methods to help ensure the reliability and reproducibility of results.
Published: 2021

24. Differential toxic effects of food contaminant mixtures in HepaRG cells after single or repeated treatments

Author: Marc Audebert, Benjamin Kopp, Ludovic Le Hégarat, Laboratoire de Fougères - ANSES, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), 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), Métabolisme et Xénobiotiques (ToxAlim-MeX), and 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)
Subjects: 0301 basic medicine, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], MESH: Mutagenicity Tests, Food Contamination, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Repeated exposure, MESH: Hepatocytes, Histones, 03 medical and health sciences, Chemical mixtures, MESH: Diet, Adverse health effect, Genetics, medicine, Humans, H2AX, Food science, Cytotoxicity, 0105 earth and related environmental sciences, Food contaminants, MESH: DNA Damage, MESH: Histones, MESH: Humans, Chemistry, Mutagenicity Tests, Low dose, Contamination, MESH: Food Contamination, MESH: Gene Expression Regulation, 3. Good health, Diet, 030104 developmental biology, Gene Expression Regulation, Liver, Mixtures, Toxicity, Hepatocytes, Genotoxicity, Food contaminant, MESH: Liver, DNA Damage
Abstract: Through diet, people are chronically exposed to low doses of a large number of contaminants that could exhibit adverse health effects. Toxicological evaluation of food contaminants increases in complexity when the exposure involves chemical mixtures. The aim of this study is to investigate the genotoxic potential, through measuring ©H2AX induction, of six common mixtures of food contaminants to which French adult consumers are chronically exposed. Mixtures were identified by combining information from consumption surveys and contaminant concentration levels in foods. Both single and repeated exposures were evaluated in human liver-derived HepaRG cells. Our results indicated that after a single 24-h exposure, only one mixture induced genotoxicity, and that response occurred at the highest concentration tested. In contrast, we observed after repeated exposures over 3 or 7 days, induction of ©H2AX for all mixtures except one, and a time- and concentration-dependent manner toxicity for four mixtures. Interestingly, we also observed a non-monotonic cytotoxicity concentration-response for one mixture, which might reflect cellular adaptation to the exposure. In conclusion, our study demonstrated that longer-term treatments for in vitro toxicological evaluation, instead of the classical 24 h treatment, may be more relevant regarding human toxicology assessment.
Published: 2019

25. Large-Scale Modeling Approach Reveals Functional Metabolic Shifts during Hepatic Differentiation

Author: Anne Corlu, Sandrine Bruel, Nicolas J. Cabaton, Fabien Jourdan, Florence Vinson, Hélène Dubois-Pot-Schneider, Clément Frainay, Cécile Canlet, Daniel Zalko, Elodie Person, Fabrice Morel, Marie-Anne Robin, Florence Maurier, Nathalie Poupin, Bernard Fromenty, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Nutrition, Métabolismes et Cancer (NuMeCan), 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 de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported in part by the French Ministry of Research and the National Research Agency, as part of the French MetaboHUB infrastructure (the National Metabolomics and Fluxomics Infrastructure, Grant ANR-INBS-0010) and the NISTEC project (Grant ANR-09-CESA-003)., ANR-09-CESA-0003,NISTEC,Nouvelles stratégies in vitro pour l'évaluation de la cytotoxicite et la genotoxicite des contaminants de l'environnement(2009), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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)-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), 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), Université de Toulouse (UT)-Université de Toulouse (UT), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-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), and 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)
Subjects: 0301 basic medicine, genome-scale metabolic modeling, [SDV]Life Sciences [q-bio], Metabolic network, Network structure, Computational biology, Biology, Models, Biological, Biochemistry, Cell Line, Omics data, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, HepaRG cell line, hepatic differentiation, Humans, Metabolomics, ComputingMilieux_MISCELLANEOUS, transcriptomics and metabolomics, Cell Differentiation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Chemistry, Phenotype, Metabolic pathway, 030104 developmental biology, Cell metabolism, Liver, Flux (metabolism), Metabolic Networks and Pathways, 030217 neurology & neurosurgery, global metabolic shifts
Abstract: International audience; Being able to explore the metabolism of broad metabolizing cells is of critical importance in many research fields. This article presents an original modeling solution combining metabolic network and omics data to identify modulated metabolic pathways and changes in metabolic functions occurring during differentiation of a human hepatic cell line (HepaRG). Our results confirm the activation of hepato-specific functionalities and newly evidence modulation of other metabolic pathways, which could not be evidenced from transcriptomic data alone. Our method takes advantage of the network structure to detect changes in metabolic pathways that do not have gene annotations and exploits flux analyses techniques to identify activated metabolic functions. Compared to the usual cell-specific metabolic network reconstruction approaches, it limits false predictions by considering several possible network configurations to represent one phenotype rather than one arbitrarily selected network. Our approach significantly enhances the comprehensive and functional assessment of cell metabolism, opening further perspectives to investigate metabolic shifts occurring within various biological contexts.
Published: 2019

26. Réflexion prospective interdisciplinaire. Approches prédictives pour la biologie et l’écologie. Rapport de synthèse

Author: Caranta, Carole, Monod, Hervé, Berry, Hugues, Chelle, Michaël, Génard, Michel, Jourdan, Fabien, Lannou, Christian, Maguin, Emmanuelle, Médale, Françoise, Oddou-Muratorio, Sylvie, Rogel Gaillard, Claire, Traas, Jan, Unité de recherche Génétique et amélioration des fruits et légumes (GAFL), Institut National de la Recherche Agronomique (INRA), UAR1203 DEPT MIA Département Mathématiques et Informatique Appliquées, Unité de recherche Plantes et Systèmes de Culture Horticoles (PSH), 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, Département Santé des Plantes et Environnement (DPT SPE), Nutrition, Métabolisme, Aquaculture (NuMéA), Institut National de la Recherche Agronomique (INRA)-Université de Pau et des Pays de l'Adour (UPPA), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, 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), Génétique et Amélioration des Fruits et Légumes (GAFL), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Toulouse III - Paul Sabatier (UT3), 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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Ecologie des Forêts Méditerranéennes (URFM), 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), INRA, UAR1203 DEPT MIA Département Mathématiques et Informatique Appliquées (devenu MathNum), 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), Université de Toulouse (UT)-Université de Toulouse (UT), and École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [INFO]Computer Science [cs]
Published: 2019

27. MetaboRank: network-based recommendation system to interpret and enrich metabolomics results

Author: Frainay, Clément, Aros, Sandrine, Chazalviel, Maxime, Garcia, Thomas, Vinson, Florence, Weiss, Nicolas, Colsch, Benoit, Sedel, Frédéric, Thabut, Dominique, Junot, Christophe, Jourdan, Fabien, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), MedDay Pharmaceuticals, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], 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), French Ministry of Research, National Research Agency as part of the French MetaboHUB, European Commission [654241], national metabolomics and fluxomics infrastructure [ANR-INBS-0010], European Project: 654241,H2020,H2020-EINFRA-2014-2,PhenoMeNal(2015), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: Systems Biology, [SDV]Life Sciences [q-bio], Computational Biology, Humans, Metabolomics, Original Papers, Mass Spectrometry, Software
Abstract: Motivation Metabolomics has shown great potential to improve the understanding of complex diseases, potentially leading to therapeutic target identification. However, no single analytical method allows monitoring all metabolites in a sample, resulting in incomplete metabolic fingerprints. This incompleteness constitutes a stumbling block to interpretation, raising the need for methods that can enrich those fingerprints. We propose MetaboRank, a new solution inspired by social network recommendation systems for the identification of metabolites potentially related to a metabolic fingerprint. Results MetaboRank method had been used to enrich metabolomics data obtained on cerebrospinal fluid samples from patients suffering from hepatic encephalopathy (HE). MetaboRank successfully recommended metabolites not present in the original fingerprint. The quality of recommendations was evaluated by using literature automatic search, in order to check that recommended metabolites could be related to the disease. Complementary mass spectrometry experiments and raw data analysis were performed to confirm these suggestions. In particular, MetaboRank recommended the overlooked α-ketoglutaramate as a metabolite which should be added to the metabolic fingerprint of HE, thus suggesting that metabolic fingerprints enhancement can provide new insight on complex diseases. Availability and implementation Method is implemented in the MetExplore server and is available at www.metexplore.fr. A tutorial is available at https://metexplore.toulouse.inra.fr/com/tutorials/MetaboRank/2017-MetaboRank.pdf. Supplementary information Supplementary data are available at Bioinformatics online.
Published: 2019

28. MetExplore: collaborative edition and exploration of metabolic networks

Author: Cottret, Ludovic, Frainay, Clément, Chazalviel, Maxime, Cabanettes, Floréal, Gloaguen, Yoann, Camenen, Etienne, Merlet, Benjamin, Heux, Stephanie, Portais, Jean-Charles, Poupin, Nathalie, Vinson, Florence, Jourdan, Fabien, Laboratoire des interactions plantes micro-organismes (LIPM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), 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), MedDay Pharmaceuticals, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Berlin Institute of Health Metabolomics Platform, Max Delbrück Center for Molecular Medicine, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Université de Toulouse (UT)-Université de Toulouse (UT), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Project Agromics from the CentreNational de laRecherche Scientifique, Wellcome Trust : 105614/Z/14/Z, INRA, ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), European Project: 654241,H2020,H2020-EINFRA-2014-2,PhenoMeNal(2015), 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-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Proteomics, Internet, Information Dissemination, [SDV]Life Sciences [q-bio], Agrobacterium, Molecular Sequence Annotation, Genomics, Saccharomyces cerevisiae, Web Server Issue, Computer Graphics, Humans, Metabolomics, Technology Platforms, Metabolic Networks and Pathways, Software
Abstract: Metabolism of an organism is composed of hundreds to thousands of interconnected biochemical reactions responding to environmental or genetic constraints. This metabolic network provides a rich knowledge to contextualize omics data and to elaborate hypotheses on metabolic modulations. Nevertheless, performing this kind of integrative analysis is challenging for end users with not sufficiently advanced computer skills since it requires the use of various tools and web servers. MetExplore offers an all-in-one online solution composed of interactive tools for metabolic network curation, network exploration and omics data analysis. In particular, it is possible to curate and annotate metabolic networks in a collaborative environment. The network exploration is also facilitated in MetExplore by a system of interactive tables connected to a powerful network visualization module. Finally, the contextualization of metabolic elements in the network and the calculation of over-representation statistics make it possible to interpret any kind of omics data. MetExplore is a sustainable project maintained since 2010 freely available at https://metexplore.toulouse.inra.fr/metexplore2/.
Published: 2018

29. An untargeted metabolomics approach to explore the metabolic modulation of HepG2 cells exposed to low doses of bisphenol A and 17β-estradiol 2

Author: Cabaton, Nicolas J., Poupin, Nathalie, Canlet, Cécile, Tremblay-Franco, Marie, Audebert, Marc, Cravedi, Jean Pierre, Riu, Anne, Jourdan, Fabien, Zalko, Daniel, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French funding program ANR (KISMET) [CESA 008 01], 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-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)-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: Bisphenol A, metabolic network analysis, Estradiol, Multivariate analysis, [SDV]Life Sciences [q-bio], HepG2 cells, Endocrine disruptors, metabolomics
Abstract: International audience; The model xeno-estrogen bisphenol A (BPA) has been extensively studied over the past two decades, contributing to major advances in the field of endocrine disrupting chemicals research. Besides its well documented adverse effects on reproduction and development observed in rodents, latest studies strongly suggest that BPA disrupts several endogenous metabolic pathways, with suspected steatogenic and obesogenic effects. BPA's adverse effects on reproduction are attributed to its ability to activate estrogen receptors (ERs), but its effects on metabolism and its mechanism(s) of action at low doses are so far only marginally understood. Metabolomics based approaches are increasingly used in toxicology to investigate the biological changes induced by model toxicants and chemical mixtures, to identify markers of toxicity and biological effects. In this study, we used proton nuclear magnetic resonance (1H-NMR) based untargeted metabolite profiling, followed by multivariate statistics and computational analysis of metabolic networks to examine the metabolic modulation induced in human hepatic cells (HepG2) by an exposure to low and very low doses of BPA (10-6M, 10-9M, and 10-12M), vs. the female reference hormone 17β-estradiol (E2, 10-9M, 10-12M, and 10-15M). Metabolomic analysis combined to metabolic network reconstruction highlighted different mechanisms at lower doses of exposure. At the highest dose, our results evidence that BPA shares with E2 the capability to modulate several major metabolic routes that ensure cellular functions and detoxification processes, although the effects of the model xeno-estrogen and of the natural hormone can still be distinguished.
Published: 2018

30. Classification of pediatric asthma: from phenotype discovery to clinical practice

Author: Ceyda Oksel, Sadia Haider, Sara Fontanella, Clement Frainay, Adnan Custovic, Oksel, Ceyda, Haider, Sadia, Custovic, Adnan, Imperial College London, Imperial Coll London, Dept Med, Sect Paediat, London, England, Partenaires INRAE, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: longitudinal data, BIG DATA, Longitudinal data, [SDV]Life Sciences [q-bio], Big data, Stability (learning theory), Review, Variation (game tree), Pediatrics, 1ST 6 YEARS, Field (computer science), 03 medical and health sciences, 0302 clinical medicine, disease progression, Medicine, 030212 general & internal medicine, CLUSTER-ANALYSIS, Immutability, Science & Technology, BIRTH COHORT, business.industry, Perspective (graphical), IGE RESPONSES, lcsh:RJ1-570, phenotypes, asthma, machine learning, big data, CHILDHOOD ASTHMA, lcsh:Pediatrics, Data science, INFLAMMATORY SUBTYPES, 3. Good health, Clinical Practice, 030228 respiratory system, ATOPY PHENOTYPES, Pediatrics, Perinatology and Child Health, WHEEZING PHENOTYPES, business, Life Sciences & Biomedicine, LATENT CLASS ANALYSIS
Abstract: International audience; Advances in big data analytics have created an opportunity for a step change in unraveling mechanisms underlying the development of complex diseases such as asthma, providing valuable insights that drive better diagnostic decision-making in clinical practice, and opening up paths to individualized treatment plans. However, translating findings from data-driven analyses into meaningful insights and actionable solutions requires approaches and tools which move beyond mining and patterning longitudinal data. The purpose of this review is to summarize recent advances in phenotyping of asthma, to discuss key hurdles currently hampering the translation of phenotypic variation into mechanistic insights and clinical setting, and to suggest potential solutions that may address these limitations and accelerate moving discoveries into practice. In order to advance the field of phenotypic discovery, greater focus should be placed on investigating the extent of within-phenotype variation. We advocate a more cautious modeling approach by "supervising" the findings to delineate more precisely the characteristics of the individual trajectories assigned to each phenotype. Furthermore, it is important to employ differentmethods within a study to compare the stability of derived phenotypes, and to assess the immutability of individual assignments to phenotypes. If we are to make a step change toward precision (stratified or personalized) medicine and capitalize on the available big data assets, we have to develop genuine cross-disciplinary collaborations, wherein data scientists who turn data into information using algorithms and machine learning, team up with medical professionals who provide deep insights on specific subjects from a clinical perspective.
Published: 2018

31. Mind the gap: mapping mass spectral databases in genome-scale metabolic networks reveals poorly covered Areas

Author: Reza M. Salek, Steffen Neumann, Oscar Yanes, Fabien Jourdan, Clément Frainay, Emma L. Schymanski, Benjamin Merlet, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Swiss Federal Insitute of Aquatic Science and Technology [Dübendorf] (EAWAG), Université du Luxembourg (Uni.lu), Department of Stress and Developmental Biology, Leibniz Institute of Plant Biochemistry (IPB), German Centre for Integrative Biodiversity Research (iDiv), International Agency for Research on Cancer (IARC), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III [Madrid] (ISC), Universitat Rovira i Virgili, Ministerio de Economia y Competitividad (MINECO) [BFU2014-57466-P], Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), an initiative of Instituto de Investigacion Carlos III (ISCIII), French Ministry of Research and National Research Agency, French MetaboHUB [ANR-INBS-0010], PhenoMeNal project, European Commission's Horizon 2020 programme [654241]., European Project: 603437,EC:FP7:ENV,FP7-ENV-2013-two-stage,SOLUTIONS(2013), 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), 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), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (Ciberdem), and Yanes, Oscar
Subjects: 0301 basic medicine, Computer science, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Genome scale, lcsh:QR1-502, metabolomics data mapping, Metabolic network, mass spectral libraries, Multidisciplinary, general & others [F99] [Life sciences], computer.software_genre, Mass spectrometry, 01 natural sciences, Biochemistry, lcsh:Microbiology, 03 medical and health sciences, Multidisciplinaire, généralités & autres [F99] [Sciences du vivant], Metabolomics, Betweenness centrality, Metabolome, Molecular Biology, Reference standards, Database, metabolite annotation, 010401 analytical chemistry, metabolic networks, 0104 chemical sciences, 030104 developmental biology, Bile acid metabolism, computer
Abstract: International audience; The use of mass spectrometry-based metabolomics to study human, plant and microbial biochemistry and their interactions with the environment largely depends on the ability to annotate metabolite structures by matching mass spectral features of the measured metabolites to curated spectra of reference standards. While reference databases for metabolomics now provide information for hundreds of thousands of compounds, barely 5% of these known small molecules have experimental data from pure standards. Remarkably, it is still unknown how well existing mass spectral libraries cover the biochemical landscape of prokaryotic and eukaryotic organisms. To address this issue, we have investigated the coverage of 38 genome-scale metabolic networks by public and commercial mass spectral databases, and found that on average only 40% of nodes in metabolic networks could be mapped by mass spectral information from standards. Next, we deciphered computationally which parts of the human metabolic network are poorly covered by mass spectral libraries, revealing gaps in the eicosanoids, vitamins and bile acid metabolism. Finally, our network topology analysis based on the betweenness centrality of metabolites revealed the top 20 most important metabolites that, if added to MS databases, may facilitate human metabolome characterization in the future.
Published: 2018

32. Genotoxicity of aflatoxins and their precursors in human cells

Author: Cécile Canlet, Marc Audebert, Olivier Puel, Isabelle P. Oswald, Selma P. Snini, Souria Tadrist, Martin G. Theumer, Laure Khoury, Yasmine Henneb, 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, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), 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-MetaToul-MetaboHUB, 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), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Métabolisme et Xénobiotiques (ToxAlim-MeX), ProdInra, Migration, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaboHUB-MetaToul, 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), and 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)
Subjects: 0301 basic medicine, Aflatoxin, Aflatoxin B1, Sterigmatocystin, [SDV]Life Sciences [q-bio], GENOTOXICITY, Anthraquinones, Toxicology, medicine.disease_cause, Activation, Metabolic, Histones, chemistry.chemical_compound, Aflatoxins, heterocyclic compounds, H2AX, Cytotoxicity, Chemistry, food and beverages, Hep G2 Cells, 04 agricultural and veterinary sciences, General Medicine, Bioquímica y Biología Molecular, 040401 food science, 3. Good health, [SDV] Life Sciences [q-bio], Biochemistry, Biological Assay, Micología, CIENCIAS NATURALES Y EXACTAS, Cell Survival, DNA damage, METABOLISM, Risk Assessment, DNA DAMAGE, Ciencias Biológicas, 03 medical and health sciences, 0404 agricultural biotechnology, medicine, Humans, Carcinogen, Dose-Response Relationship, Drug, Mutagenicity Tests, genotoxicity, technology, industry, and agriculture, aflatoxin, Metabolism, biological factors, AFLATOXIN, 030104 developmental biology, Cell culture, metabolism, Biomarkers, Genotoxicity
Abstract: Aflatoxins are found as food contaminant and some of them demonstrate a carcinogenic effect. The aflatoxins biosynthetic pathway involves 15 successive steps. The aim of this study was to compare the toxicity of aflatoxins and their precursors in three human cell lines. We tested the four aflatoxins and two of their metabolites; three early metabolic precursors and two late biosynthetic precursors. Cyclopiazonic acid, synthesized in parallel with aflatoxins, was also tested. The cytotoxicity and the genotoxicity was evaluated with the γH2AX assay in three human cell lines with different bioactivation capacities. Our results indicated that the most genotoxic chemicals in the three cell lines were in decreasing order sterigmatocystin (ST), aflatoxin B1 (AFB1), aflatoxicol (AFL), aflatoxin G1 (AFG1) and versicolorin A (VERA). Aflatoxin M1 (AFM1) demonstrated genotoxic property in only one cell line. The other tested compounds did not demonstrate any genotoxic activity. Overall, our results suggested different genotoxic mechanisms of action for the tested compounds, involving specific bioactivation pathways. Moreover, some metabolic precursors of aflatoxins demonstrated genotoxic potential equivalent or greater to AFB1. This should be taking into account for the development of new strategies intended to reduce the aflatoxins exposure and for human risk assessment. Fil: Theumer, Martín Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Université de Toulouse; Francia. Institut National de la Recherche Agronomique; Francia Fil: Henneb, Y.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Khoury, L.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Snini, S.P.. Université de Toulouse; Francia. Institut National de la Recherche Agronomique; Francia Fil: Tadrist, S.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Canlet, C.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Puel, O.. Université de Toulouse; Francia. Institut National de la Recherche Agronomique; Francia Fil: Oswald, I.P.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Audebert, M.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia
Published: 2018

33. Epigenetic effects of low perinatal doses of flame retardant BDE-47 on mitochondrial and nuclear genes in rat offspring

Author: Elena Colicino, Daniel Zalko, Andrea A. Baccarelli, Larissa Takser, Maria Chiara Frisardi, Nora Benachour, Hyang-Min Byun, Harvard School of Public Health, Université de Sherbrooke (UdeS), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Department of Environmental Health, ANSES (Agence nationale de securite sanitaire de l'alimentation, de l'environnement et du travail, France) [EST-08-46], FRQ-S, CIHR (the Canadian Institutes of Health Research), FRQS (Fonds de Recherche du Quebec - Sante), and United States National Institute of Environmental Health Sciences [R21ES022694, ES021357, ES021733]
Subjects: Male, medicine.medical_specialty, Nuclear gene, Offspring, [SDV]Life Sciences [q-bio], Gestational Age, Mitochondrion, Biology, Toxicology, DNA, Mitochondrial, Article, Epigenesis, Genetic, Polybrominated diphenyl ethers, Pregnancy, Internal medicine, Halogenated Diphenyl Ethers, medicine, Animals, Epigenetics, Rats, Wistar, Flame Retardants, Cell Nucleus, Perinatal Exposure, Age Factors, Gene Expression Regulation, Developmental, DNA Methylation, Frontal Lobe, Mitochondria, 3. Good health, Interspersed Repetitive Sequences, Endocrinology, Maternal Exposure, Prenatal Exposure Delayed Effects, DNA methylation, Toxicity, Female
Abstract: International audience; Polybrominated diphenyl ethers (PBDEs) are known endocrine disrupting chemicals used commonly as flame retardants in everything from electronics to furniture. Exposure to PBDEs during early development has been linked to neurodevelopmental delays. Despite mounting evidence of neurological harm from PBDE exposure, the molecular mechanisms underlying these effects on brain function remain unknown. We examined the effects of perinatal exposure to BDE-47, the most biologically active and prevalent BDE congener in North America, on epigenetic patterns in the frontal lobe of Wistar rats. Dams were gavaged with BDE-47 (0.002 and 0.2 mg/kg body weight) at gestation days 9 and 16, and postnatal days 1, 8, and 15. Frontal lobes from offspring at postnatal day 41 were collected to measure 5-methylcytosine (5mC) in mitochondrial cytochrome c oxidase genes (Mt-co1,Mt-co2, and Mt-co3), global nuclear 5-hydroxymethylcytosine (5hmC) content, 5mC in repetitive elements L1Rn, and 5mC in nuclear genes (Bdnf, Crhr1, Mc2r, Nr3c1, and Snca) related to behavioral and brain functions in the nuclear genome. We observed a significant decrease in %5mC in Mt-co2 (difference from control=-0.68%, p=0.01 at the 0.2 mg/kg BDE-47). 5mC in repetitive elements L1Rn decreased at 0.002 mg/kg BDE-47 (difference=-1.23%, p=0.02). Decreased nuclear 5mC was observed in Bdnf and Nr3c1 in BDE-47 exposed rats. However, we did not observe significant effects of PBDE toxicity on DNA methylation patterns for the majority of genes in the brain.
Published: 2015

34. TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei

Author: Shameer, Sanu, Logan-Klumpler, Flora J, Vinson, Florence, Cottret, Ludovic, Merlet, Benjamin, Achcar, Fiona, Boshart, Michael, Berriman, Matthew, Breitling, Rainer, Bringaud, Frédéric, Bütikofer, Peter, Cattanach, Amy M, Bannerman-Chukualim, Bridget, Creek, Darren J, Crouch, Kathryn, de Koning, Harry P, Denise, Hubert, Ebikeme, Charles, Fairlamb, Alan H, Ferguson, Michael A J, Ginger, Michael L, Hertz-Fowler, Christiane, Kerkhoven, Eduard J, Mäser, Pascal, Michels, Paul A M, Nayak, Archana, Nes, David W, Nolan, Derek P, Olsen, Christian, Silva-Franco, Fatima, Smith, Terry K, Taylor, Martin C, Tielens, Aloysius G M, Urbaniak, Michael D, van Hellemond, Jaap J, Vincent, Isabel M, Wilkinson, Shane R, Wyllie, Susan, Opperdoes, Fred R, Barrett, Michael P, Jourdan, Fabien, LS Biochemie van parasieten, B&C BRC-SIB-TR, Regenerative Medicine, Stem Cells & Cancer, Medical Microbiology & Infectious Diseases, LS Biochemie van parasieten, B&C BRC-SIB-TR, Regenerative Medicine, Stem Cells & Cancer, 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), The Wellcome Trust Sanger Institute [Cambridge], Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Laboratoire des interactions plantes micro-organismes (LIPM), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), University of Glasgow, Ludwig Maximilians University of Munich, University of Manchester [Manchester], Centre National de la Recherche Scientifique (CNRS), University of Bern, Monash University, European Molecular Biology Laboratory European Bioinformatics Institute, United Nations Educational, Scientific and Cultural Organization (UNESCO), University of Dundee, Lancaster University, University of Liverpool, Chalmers University of Technology [Gothenburg, Sweden], Swiss Tropical and Public Health Institute [Basel], University of Edinburgh, TexasTech University, Trinity College Dublin, Biomatters Inc, Partenaires INRAE, University of St Andrews [Scotland], London School of Hygiene and Tropical Medicine (LSHTM), Utrecht University [Utrecht], Erasmus University Rotterdam, Queen Mary University of London (QMUL), Université Catholique de Louvain = Catholic University of Louvain (UCL), ANR project, European Project: 290080,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,PARAMET(2012), University of St Andrews. School of Biology, University of St Andrews. Biomedical Sciences Research Complex, 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), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Ludwig-Maximilians University [Munich] (LMU)
Subjects: Proteomics, Anabolism, QH301 Biology, [SDV]Life Sciences [q-bio], Trypanosoma brucei brucei, Metabolic network, 610 Medicine & health, Biology, Trypanosoma brucei, computer.software_genre, 03 medical and health sciences, QH301, Metabolomics, Metabolome, Genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Database Issue, Data Mining, 030304 developmental biology, base de données, 0303 health sciences, Internet, Database, Catabolism, 030302 biochemistry & molecular biology, DAS, métabolisme cellulaire, biology.organism_classification, maladie parasitaire, QR, Metabolic pathway, 570 Life sciences, biology, computer, trypanosoma brucei, Databases, Chemical, Metabolic Networks and Pathways
Abstract: European Commission FP7 Marie Curie Initial Training Network ‘ParaMet’ [290080 to S.S.]; ANR project MetaboHub [ANR-11-INBS-0010 to B.M.]; Wellcome Trust [085349]; The work of Fiona Achcar was part of the SysMO SilicoTryp project coordinated by R.B. Funding for open access charge: European Commission FP7 Marie Curie Initial Training Network ‘ParaMet’ [290080]. The metabolic network of a cell represents the catabolic and anabolic reactions that interconvert small molecules (metabolites) through the activity of enzymes, transporters and non-catalyzed chemical reactions. Our understanding of individual metabolic networks is increasing as we learn more about the enzymes that are active in particular cells under particular conditions and as technologies advance to allow detailed measurements of the cellular metabolome. Metabolic network databases are of increasing importance in allowing us to contextualise data sets emerging from transcriptomic, proteomic and metabolomic experiments. Here we present a dynamic database, TrypanoCyc (http://www.metexplore.fr/trypanocyc/), which describes the generic and condition-specific metabolic network of Trypanosoma brucei, a parasitic protozoan responsible for human and animal African trypanosomiasis. In addition to enabling navigation through the BioCyc-based TrypanoCyc interface, we have also implemented a network-based representation of the information through MetExplore, yielding a novel environment in which to visualise the metabolism of this important parasite. Publisher PDF
Published: 2015

35. In vitro and in vivo estrogenic activity of BPA, BPF and BPS in zebrafish-specific assays

Author: Vincent Le Fol, Selim Ait-Aissa, Jean-Marc Porcher, Jean Pierre Cravedi, Manoj Sonavane, Patrick Balaguer, Daniel Zalko, François Brion, 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 National de l'Environnement Industriel et des Risques (INERIS), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), French Ministry of Ecology (P181-DRC50), FP7-PEOPLE-2011-ITN EDAEMERGE project under the grant agreement number 290100, 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, Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Male, Embryo, Nonmammalian, Health, Toxicology and Mutagenesis, pertubateur endocrinien, [SDV]Life Sciences [q-bio], brachydanio rerio, toxicologie alimentaire, Estrogen receptor, 010501 environmental sciences, Endocrine Disruptors, human health, 01 natural sciences, Green fluorescent protein, Animals, Genetically Modified, chemistry.chemical_compound, Vitellogenins, Genes, Reporter, Sulfones, Aromatase, Zebrafish, biology, zebrafish, endocrine disruptors, bisphenols, estrogenic activity, MESH: Animals, Genetically Modified, Aromatase/metabolism, Brain/drug effects, Cell Line, Brain, General Medicine, santé humaine, Pollution, Cell biology, Receptors, Estrogen, [SDE]Environmental Sciences, bisphénol s, oestrogénicité, Biological Assay, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, endocrine system, Green Fluorescent Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Vitellogenin, Phenols, In vivo, Internal medicine, medicine, bisphénol a, Animals, Benzhydryl Compounds, 0105 earth and related environmental sciences, urogenital system, Public Health, Environmental and Occupational Health, Estrogens, Zebrafish Proteins, biology.organism_classification, In vitro, 030104 developmental biology, Endocrinology, Bisphenol S, chemistry, biology.protein
Abstract: International audience; Bisphenol A (BPA) is a widely used chemical that has been extensively studied as an endocrine-disrupting chemical (EDC). Other bisphenols sharing close structural features with BPA, are increasingly being used as alternatives, increasing the need to assess associated hazards to the endocrine system. In the present study, the estrogenic activity of BPA, bisphenol S (BPS) and bisphenol F (BPF) was assessed by using a combination of zebrafish-specific mechanism-based in vitro and in vivo assays. The three bisphenols were found to efficiently transactivate all zebrafish estrogen receptor (zfER) subtypes in zebrafish hepatic reporter cell lines (ZELH-zfERs). BPA was selective for zfERα while BPS and BPF were slightly more potent on zfERβ subtypes. We further documented the estrogenic effect in vivo by quantifying the expression of brain aromatase using a transgenic cyp19a1b-GFP zebrafish embryo assay. All three bisphenols induced GFP in a concentration-dependent manner. BPS only partially induced brain aromatase at the highest tested concentrations (>30µM) while BPA and BPF strongly induced GFP, in an ER-dependent manner, at 1-10µM. Furthermore, we show that BPF strongly induced vitellogenin synthesis in adult male zebrafish. Overall, this study demonstrates the estrogenic activity of BPA, BPF and BPS in different cell- and tissue-contexts and at different stages of development. Differences between in vitro and in vivo responses are discussed in light of selective ER activation and the fate of the compounds in the models. This study confirms the relevance of combining cellular and whole-organism bioassays in a unique model species for the hazard assessment of candidate EDCs.
Published: 2017

36. Role of phase I and II metabolic enzymes in the metabolic activation of heterocyclic amines genotoxins

Author: Marc Audebert, Matthieu Chevereau, Glatt, H., Jean Pierre Cravedi, Daniel Zalko, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), and German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: 48th Annual Meeting of the Environmental-Mutagenesis-and-Genomics-Society (EMGS) on Environmental Health Sciences Bridging the Gap between Exposure, Mechanism and Public Health, Raleigh, 09-13 septembre 2017; International audience
Published: 2017

37. AKT2 suppresses pro-survival autophagy triggered by DNA double-strand breaks in colorectal cancer cells

Author: Jörg Fahrer, Teresa Frisan, Bernd Kaina, Mahmoud Toulany, Carina Neitzel, Marc Audebert, Nina Seiwert, Svenja Stroh, Department of Toxicology, University of Cagliari, Department of Cell and Molecular Biology, Karolinska Institutet [Stockholm], 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), Department of Radiation Oncology, Division of Radiobiology and Molecular Environmental Research, University of Tuebingen, German Cancer Consortium, Johannes Gutenberg - Universität Mainz (JGU), Justus-Liebig-Universität Gießen (JLU), Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden, Partenaires INRAE, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, and Fahrer, Jörg
Subjects: 0301 basic medicine, Cancer Research, Programmed cell death, autophagy, appareil intestinal, DNA damage, [SDV]Life Sciences [q-bio], Immunology, ATG5, Bacterial Toxins, Ataxia Telangiectasia Mutated Proteins, autophagie, Biology, Transfection, human health, akt2, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Downregulation and upregulation, cellule intestinale, Cell Line, Tumor, Humans, DNA Breaks, Double-Stranded, Protein kinase B, ComputingMilieux_MISCELLANEOUS, différenciation cellulaire, Autophagy, Cell Biology, santé humaine, HCT116 Cells, 3. Good health, Cell biology, 030104 developmental biology, Apoptosis, cancer colorectal, 030220 oncology & carcinogenesis, Gene Knockdown Techniques, Cancer research, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Original Article, Signal transduction, Tumor Suppressor Protein p53, Colorectal Neoplasms, colorectal neoplasm, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract: DNA double-strand breaks (DSBs) are critical DNA lesions, which threaten genome stability and cell survival. DSBs are directly induced by ionizing radiation (IR) and radiomimetic agents, including the cytolethal distending toxin (CDT). This bacterial genotoxin harbors a unique DNase-I-like endonuclease activity. Here we studied the role of DSBs induced by CDT and IR as a trigger of autophagy, which is a cellular degradation process involved in cell homeostasis, genome protection and cancer. The regulatory mechanisms of DSB-induced autophagy were analyzed, focusing on the ATM-p53-mediated DNA damage response and AKT signaling in colorectal cancer cells. We show that treatment of cells with CDT or IR increased the levels of the autophagy marker LC3B-II. Consistently, an enhanced formation of autophagosomes and a decrease of the autophagy substrate p62 were observed. Both CDT and IR concomitantly suppressed mTOR signaling and stimulated the autophagic flux. DSBs were demonstrated as the primary trigger of autophagy using a DNase I-defective CDT mutant, which neither induced DSBs nor autophagy. Genetic abrogation of p53 and inhibition of ATM signaling impaired the autophagic flux as revealed by LC3B-II accumulation and reduced formation of autophagic vesicles. Blocking of DSB-induced apoptotic cell death by the pan-caspase inhibitor Z-VAD stimulated autophagy. In line with this, pharmacological inhibition of autophagy increased cell death, while ATG5 knockdown did not affect cell death after DSB induction. Interestingly, both IR and CDT caused AKT activation, which repressed DSB-triggered autophagy independent of the cellular DNA-PK status. Further knockdown and pharmacological inhibitor experiments provided evidence that the negative autophagy regulation was largely attributable to AKT2. Finally, we show that upregulation of CDT-induced autophagy upon AKT inhibition resulted in lower apoptosis and increased cell viability. Collectively, the findings demonstrate that DSBs trigger pro-survival autophagy in an ATM- and p53-dependent manner, which is curtailed by AKT2 signaling.
Published: 2017

38. Role of human sulfotransferase 1A1 and N-acetyltransferase 2 in the metabolic activation of 16 heterocyclic amines and related heterocyclics to genotoxicants in recombinant V79 cells

Author: Matthieu Chevereau, Daniel Zalko, Marc Audebert, Jean-Pierre Cravedi, Hansruedi Glatt, 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), Department of Nutritional Toxicology, German Institute of Human Nutrition, Department of Food Safety, Bundesinstitut für Risikobewertung - Federal Institute for Risk Assessment (BfR), Métabolisme et Xénobiotiques (ToxAlim-MeX), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: 0301 basic medicine, Sulfotransferase, Arylamine N-Acetyltransferase, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Sulfotransferase 1A1, Toxicology, medicine.disease_cause, Activation, Metabolic, 03 medical and health sciences, V79 cells, Cytochrome P-450 CYP1A2, Heterocyclic Compounds, Quinoxalines, medicine, Animals, Humans, H2AX, Carcinogen, chemistry.chemical_classification, biology, Mutagenicity Tests, Chemistry, genotoxicity, Imidazoles, CYP1A2, Cytochrome P450, General Medicine, Metabolism, heterocyclic aromatic amines, Arylsulfotransferase, Recombinant Proteins, 030104 developmental biology, Enzyme, Biochemistry, biology.protein, metabolism, Genotoxicity, Mutagens
Abstract: Heterocyclic aromatic amines (HAAs) are primarily produced during the heating of meat or fish. HAAs are mutagenic and carcinogenic, and their toxicity in model systems depend on metabolic activation. This activation is mediated by cytochrome P450 (CYP) enzymes, in particular CYP1A2. Some studies have indicated a role of human sulfotransferase (SULT) 1A1 and N-acetyltransferase (NAT) 2 in the terminal activation of HAAs. In this study, we conducted a metabolism/genotoxicity relationship analysis for 16 HAAs and related heterocyclics. We used the γH2AX genotoxicity assay in V79 cells (deficient in CYP, SULT and NAT) and V79-derived cell lines genetically engineered to express human CYP1A2 alone or in combination with human SULT1A1 or NAT2. Our data demonstrated genotoxic properties for 13 out of the 16 compounds tested. A clear relationship between metabolic bioactivation and genotoxicity allowed to distinguish four groups: (1) Trp-P-1 genotoxicity was linked to CYP1A2 bioactivation only—with negligible effects of phase II enzymes; (2) Glu-P-2, Glu-P-1, Trp-P-2, APNH, MeAαC and AαC were bioactivated by CYP1A2 in combination with either phase II enzyme tested (NAT2 or SULT1A1); (3) IQ, 4-MeIQ, IQx, 8-MeIQx, and 4,8-DiMeIQx required CYP1A2 in combination with NAT2 to be genotoxic, whereas SULT1A1 did not enhance their genotoxicity; (4) PhIP became genotoxic after CYP1A2 and SULT1A1 bioactivation—NAT2 had not effect. Our results corroborate some previous data regarding the genotoxic potency of seven HAAs and established the genotoxicity mechanism for five others HAAs. This study also permits to compare efficiently the genotoxic potential of these 13 HAAs.
Published: 2017

39. Characterization of xenobiotic metabolizing enzymes of a reconstructed human epidermal model from adult hair follicles

Author: Daniel Bacqueville, Hélène Duplan, Emilien L. Jamin, Laure Duprat, Sandrine Bessou-Touya, Daniel Zalko, Elisabeth Perdu, Carine Jacques, Béatrice Guiraud, Département Pharmacologie, Service Pharmacologie Division 2 et Pharmacocinétique Cutané, Pierre Fabre Dermo-cosmétique, Centre de Recherche Pierre Fabre, 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 Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), 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-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), 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)-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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, 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), Bacqueville, Daniel, 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), and 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)
Subjects: 0301 basic medicine, Keratinocytes, [SDV]Life Sciences [q-bio], Aldehyde dehydrogenase, Human skin, Toxicology, Outer root sheath, Ligands, human health, HSD17B10, Substrate Specificity, Cytochrome P-450 Enzyme System, Gene expression, Basic Helix-Loop-Helix Transcription Factors, Cells, Cultured, Glutathione Transferase, chemistry.chemical_classification, Cytochrome P-450 Enzyme Inducers, tissu cutané, biology, integumentary system, hair follicle, coat, épiderme, santé humaine, enzyme du métabolisme des xénobiotiques, Isoenzymes, cutaneous metabolism, medicine.anatomical_structure, Biochemistry, Enzyme Induction, dermatologie, Sulfotransferases, expression des gènes, reconstructed human epidermis, gene expression, functional activity, Xenobiotics, 03 medical and health sciences, medicine, Humans, Pharmacology, Metabolism, Hair follicle, Metabolic Detoxication, Phase II, Kinetics, 030104 developmental biology, Enzyme, chemistry, Receptors, Aryl Hydrocarbon, peau, biology.protein, Metabolic Detoxication, Phase I, cheveu
Abstract: In this study, a comprehensive characterization of xenobiotic metabolizing enzymes (XMEs) based on gene expression and enzyme functionality was made in a reconstructed skin epidermal model derived from the outer root sheath (ORS) of hair follicles (ORS-RHE). The ORS-RHE model XME gene profile was consistent with native human skin. Cytochromes P450 (CYPs) consistently reported to be detected in native human skin were also present at the gene level in the ORS-RHE model. The highest Phase I XME gene expression levels were observed for alcohol/aldehyde dehydrogenases and (carboxyl) esterases. The model was responsive to the CYP inducers, 3-methylcholanthrene (3-MC) and β-naphthoflavone (βNF) after topical and systemic applications, evident at the gene and enzyme activity level. Phase II XME levels were generally higher than those of Phase I XMEs, the highest levels were GSTs and transferases, including NAT1. The presence of functional CYPs, UGTs and SULTs was confirmed by incubating the models with 7-ethoxycoumarin, testosterone, benzo(a)pyrene and 3-MC, all of which were rapidly metabolized within 24h after topical application. The extent of metabolism was dependent on saturable and non-saturable metabolism by the XMEs and on the residence time within the model. In conclusion, the ORS-RHE model expresses a number of Phase I and II XMEs, some of which may be induced by AhR ligands. Functional XME activities were also demonstrated using systemic or topical application routes, supporting their use in cutaneous metabolism studies. Such a reproducible model will be of interest when evaluating the cutaneous metabolism and potential toxicity of innovative dermo-cosmetic ingredients.
Published: 2017

40. Gestion territoriale de l'azote - Réaménager : Le paysage est-il une solution ?

Author: Laurent, Francois, Drouet, Jean-Louis, 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), Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris-Saclay, Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and ProdInra, Archive Ouverte
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: Gestion territoriale de l'azote - Réaménager : Le paysage est-il une solution ?
Published: 2017

41. MetaNetter 2: A Cytoscape plugin for ab initio network analysis and metabolite feature classification

Author: Burgess, K.E.V., Borutzki, Y., Rankin, N., Daly, R., Jourdan, S., University of Glasgow, Institute of Infection, Immunity and Inflammation, Institute of Cardiovascular and Medical Sciences, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Staphylococcus aureus, Databases, Factual, Mass spectrometry, MetaNetter, [SDV]Life Sciences [q-bio], Computational Biology, Ab-initio network, metabolomics, ab-initio network, Aerobiosis, Article, metaNetter, Metabolomics, Anaerobiosis, Software, mass spectrometry
Abstract: Highlights • An update to the ab-initio network construction tool MetaNetter has been produced. • The tool creates networks of masses from high resolution mass spectrometry data. • The new plugin provides both chemical transformation and adduct mapping. • Tables mapping adduct and transform counts across samples can be generated. • Retention time windows are supported for both adduct and transform network generation., Metabolomics frequently relies on the use of high resolution mass spectrometry data. Classification and filtering of this data remain a challenging task due to the plethora of complex mass spectral artefacts, chemical noise, adducts and fragmentation that occur during ionisation and analysis. Additionally, the relationships between detected compounds can provide a wealth of information about the nature of the samples and the biochemistry that gave rise to them. We present a biochemical networking tool: MetaNetter 2 that is based on the original MetaNetter, a Cytoscape plugin that creates ab initio networks. The new version supports two major improvements: the generation of adduct networks and the creation of tables that map adduct or transformation patterns across multiple samples, providing a readout of compound relationships. We have applied this tool to the analysis of adduct patterns in the same sample separated under two different chromatographies, allowing inferences to be made about the effect of different buffer conditions on adduct detection, and the application of the chemical transformation analysis to both a single fragmentation analysis and an all-ions fragmentation dataset. Finally, we present an analysis of a dataset derived from anaerobic and aerobic growth of the organism Staphylococcus aureus demonstrating the utility of the tool for biological analysis.
Published: 2016

42. Disposition of fipronil in rats

Author: G. Delous, Daniel Zalko, Catherine Viguié, Laurent Debrauwer, Jean Pierre Cravedi, 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 Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French Ministry of Ecology and Sustainable Development [PNRPE 000042], Midi Pyrenees region [08004686, 09006143], 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-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)-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: Male, Insecticides, Environmental Engineering, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, Metabolite, Adipose tissue, Urine, 010501 environmental sciences, Pharmacology, 01 natural sciences, Hydroxylation, 03 medical and health sciences, chemistry.chemical_compound, In vivo, medicine, Animals, Environmental Chemistry, Tissue Distribution, Phenylpyrazoles, Biotransformation, Fipronil, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, Kidney, Public Health, Environmental and Occupational Health, General Medicine, General Chemistry, Metabolism, Glucuronic acid, Pollution, Rats, 3. Good health, Pesticide, medicine.anatomical_structure, chemistry, Pyrazoles
Abstract: International audience; In the scientific literature, little attention has been paid to the disposition of fipronil, a phenyl pyrazole insecticide. In this study, the tissue distribution, the metabolic fate, and the elimination of fipronil was investigated in rats using radiolabeled fipronil. When a single oral dose of (14)C-fipronil (10 mg kg(-1) b.w.) was given to rats, the proportion of dose eliminated in urine and feces 72 h after dosing was ca 4% for each route. At the end of the experiment the highest levels of radioactivity were found in adipose tissue and adrenals. The main part of the radioactivity present in investigated tissues (adipose tissue, adrenals, liver, kidney, testes) was due to fipronil-sulfone. Five additional metabolites, isolated from urine were characterized by LC-MS/MS. Most of them are formed by the loss of the trifluoromethylsulphinyl group and subsequent hydroxylation and/or conjugation to glucuronic acid or sulfate. In conclusion, the retention of the metabolite fipronil sulfone in tissues following fipronil administration raises the question of the potential toxicity of this insecticide.
Published: 2013

43. Antioxidant properties of tea blunt ROS-dependent lipogenesis: beneficial effect on hepatic steatosis in a high fat-high sucrose diet NAFLD obese rat model

Author: Roger Rahmani, Jean-Michel Maixent, Georges de Sousa, Martine Armand, Grégory Meyer, Sylvain Battault, Catherine Riva, Alessandro R. Nascimento, Sandrine Gaillard, Cyril Reboul, Laura Braud, Processus de Transfert et d'Echanges dans l'Environnement - EA 3819 (PROTEE), Université de Toulon (UTLN), EA4278 Laboratoire de Pharm-Ecologie Cardiovasculaire (LaPEC), Avignon Université (AU), Laboratoire de neurobiologie et pharmacologie cardiovasculaire (LNPCV), Université de Strasbourg (UNISTRA), Plateforme Technologique BioTechServices, 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 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), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Bourg-en-Bresse, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Physiopathologie des adaptations cardiovasculaires à l'Exercice, Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: 0301 basic medicine, Mitochondrial ROS, Male, Antioxidant, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Clinical Biochemistry, medicine.disease_cause, Biochemistry, Antioxidants, Camellia sinensis, chemistry.chemical_compound, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, Nutrition and Dietetics, Superoxide, 3. Good health, 030220 oncology & carcinogenesis, Lipogenesis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Obesogenic diet, medicine.medical_specialty, Oxidative phosphorylation, Diet, High-Fat, 03 medical and health sciences, Antilipogenesis, Internal medicine, NAFLD, medicine, Animals, Obesity, Rats, Wistar, Molecular Biology, Reactive oxygen species, Tea, business.industry, medicine.disease, Disease Models, Animal, Oxidative Stress, 030104 developmental biology, Endocrinology, chemistry, Hepatocytes, Lipid Peroxidation, Steatosis, business, Reactive Oxygen Species, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Oxidative stress
Abstract: International audience; Oxidative stress could trigger lipid accumulation in liver and thus hepatic steatosis. Tea is able to prevent liver disorders, but a direct link between antioxidant capacities and prevention of steatosis has not been reported yet. We aimed to investigate such relationship in a rat model of high fat-high sucrose diet (HFS)-induced obesity and to explore more deeply the mechanisms in isolated hepatocytes. Wistar rats were divided into a control group (standard diet), an HFS group (high fat-sucrose diet) and an HFS+tea group (HFS diet with ad-libitum access to tea drink). Body weight, fat mass, glycemic parameters in blood, lipid and oxidative stress parameters in blood and liver were measured in each group after 14 weeks. Isolated hepatocytes were treated with the reactive oxygen species (ROS) inducer t-BHP in the presence or not of antioxidants (tempol or tea), and superoxide anion production and lipid accumulation were measured using specific fluorescent probes. We reported that the HFS diet highly increased hepatic lipids content, while tea consumption attenuated steatosis and improved the oxidative status (decrease in hepatic oxidative stress, increase in plasma total antioxidant capacity). The role of antioxidant properties of tea in such phenomenon was confirmed in primary cultured rat hepatocytes. Indeed, the increase of mitochondrial ROS production with t-BHP resulted in lipid accumulation in hepatocytes (positive linear regression), and antioxidants (tempol or tea) normalized both. We reported that the antioxidant properties of tea protect rats from an obesogenic HFS diet-induced hepatic steatosis by counteracting the ROS-dependent lipogenesis.
Published: 2016

44. Exploring the interplay between the cental nervous and endocrine systems for identifying biomarkers of effect of developmental exposure to endocrine disruptors: a sheep point of view

Author: Catherine Viguié, Davy Guignard, Gayrard-Troy, Véronique V., Nicole Picard-Hagen, Daniel Zalko, Cabaton, Nicolas J., Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), 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, Métabolisme et Xénobiotiques (ToxAlim-MeX), and British Society for Neuroendocrinology (BSN). Glasgow, GBR.
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

45. CT Imaging Assessment of Response to Treatment in Chronic Pulmonary Aspergillosis

Author: Cendrine Godet, François Laurent, Anne Bergeron, Pierre Ingrand, Catherine Beigelman-Aubry, Boubou Camara, Vincent Cottin, Patrick Germaud, Bruno Philippe, Christophe Pison, Cécile Toper, Marie France Carette, Jean-Pierre Frat, Guillaume Béraud, France Roblot, Jacques Cadranel, Antoine Khalil, Pascal Blouin, Institut Universitaire de Santé Publique [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Univ Hosp Poitiers, Dept Infect Dis, 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), Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Pitié-Salpêtrière [APHP], Department of Pneumology [Lyon], Hospices Civils de Lyon (HCL), Service de Pneumologie, Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut du Thorax, Université de Bordeaux (UB), Santé publique : épidémiologie et qualité des soins-EA 2694 (CERIM), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service des Maladies Infectieuses, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital de La Milétrie, Service de pneumologie et réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Service de pneumologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Clinique de pneumologie, CHU Grenoble, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Nantes (UN)-Institut du Thorax-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pfizer (Paris, France), ASTELLAS Pharma SAS (France), SOS Oxygene (Nice, France), ISIS Medical (France), AADAIRC (Poitou-Charentes, France), 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), Université de Toulouse (UT)-Université de Toulouse (UT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Antifungal Agents, Concordance, [SDV]Life Sciences [q-bio], 030106 microbiology, Treatment outcome, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, chronic pulmonary aspergillosis, Humans, Medicine, Serologic Tests, Aged, Retrospective Studies, business.industry, Chronic pulmonary aspergillosis, Reproducibility of Results, Retrospective cohort study, Middle Aged, medicine.disease, Response to treatment, 3. Good health, Clinical trial, 030228 respiratory system, Chronic Disease, treatment outcome, Female, France, Pulmonary Aspergillosis, Radiology, Drug Monitoring, Ct imaging, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, Wall thickness, business, radiologic response, CT
Abstract: Long-term antifungal therapy is usually the only treatment option for chronic pulmonary aspergillosis. However, response rates are difficult to compare because the reported clinical, mycologic, or radiologic criteria are not standardized. Objective parameters are therefore needed. To define the most relevant CT imaging variables in assessment of response to treatment, we investigated changes over time in CT imaging variables.Changes in CT imaging variables were assessed by systematic analysis of the CT scan findings of 36 patients at diagnosis and 6 months after initiation of treatment. The relevant radiologic variables were determined by selecting those showing significant changes over time. Two experienced thoracic radiologists, blinded for clinical and serologic response, independently performed CT scan analyses. Interreader agreement and concordance between radiologic and clinical response were evaluated.Of the 36 patients, seven experienced clinical deterioration while undergoing therapy. Significantly evolving radiologic variables included cavity and pleural wall thickening (P .05), which were associated with clinical improvement. There was a strong association between fungus ball disappearance and cavity/pleural wall thickening reduction and clinical improvement (P = .04). There was poor agreement between size changes of cavities or nodules, and clinical evolution (Cohen's κ, -0.13 to -0.24).Variations in cavity and pleural wall thickness may be the most relevant CT imaging variables for assessing response to treatment. Loss of fungus ball is strongly associated with clinical and radiologic improvement, but cavity size changes are unrelated to chronic pulmonary aspergillosis evolution. All these CT imaging variables may be applied in future clinical trials to assess treatment outcome.
Published: 2016

46. Uppsala Consensus Statement on Environmental Contaminants and the Global Obesity Epidemic

Author: Linda S. Birnbaum, Hong Kyu Lee, Laura N. Vandenberg, Lars Lind, Marlene Ågerstrand, Åke Bergman, Angel Nadal, Linda Dunder, Margareta Halin Lejonklou, P. Monica Lind, Youngmi Kim Pak, Carlos Guerrero-Bosagna, Juliette Legler, Erik Lampa, Mattias Öberg, Jerrold J. Heindel, Daniel Zalko, Bruce Blumberg, Richard P. Phipps, Uppsala University, Toxicology Sciences Research Center, Partenaires INRAE, Linköping University (LIU), Uppsala Clinical Research Center, Eulji University, Institute for Environmental Studies, University of Amsterdam [Amsterdam] (UvA), Universidad Miguel Hernández [Elche] (UMH), Kyung Hee University (KHU), University of Rochester [USA], University of Massachusetts System (UMASS), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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, Stockholm University, University of California [Irvine] (UCI), University of California, National Institute of Environmental Health Sciences [Durham] (NIEHS-NIH), National Institutes of Health [Bethesda] (NIH), and Lind, Lars
Subjects: 0301 basic medicine, FOOD-INTAKE, Statement (logic), Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Consensus Development Conferences as Topic, education, ENDOCRINE-DISRUPTING CHEMICALS, MEDLINE, 030209 endocrinology & metabolism, Toxicology, Global Health, Medical and Health Sciences, 03 medical and health sciences, Arbetsmedicin och miljömedicin, 0302 clinical medicine, Environmental health, medicine, Global health, Humans, PERSISTENT ORGANIC POLLUTANTS, Obesity, Epidemics, PRENATAL EXPOSURE, Sweden, OVERWEIGHT, business.industry, Public Health, Environmental and Occupational Health, Tvärvetenskapliga studier inom samhällsvetenskap, Occupational Health and Environmental Health, BISPHENOL-A, MICE, WEIGHT, PREGNANCY, INSULIN, medicine.disease, 3. Good health, 030104 developmental biology, Environmental Pollutants, Social Sciences Interdisciplinary, business, Brief Communications, Environmental Health, Environmental Sciences
Abstract: International audience; From the lectures presented at the 2nd International Workshop on Obesity and Environmental Contaminants, which was held in Uppsala, Sweden, on 8-9 October 2015, it became evident that the findings from numerous animal and epidemiological studies are consistent with the hypothesis that environmental contaminants could contribute to the global obesity epidemic. To increase awareness of this important issue among scientists, regulatory agencies, politicians, chemical industry management, and the general public, the authors summarize compelling scientific evidence that supports the hypothesis and discuss actions that could restrict the possible harmful effects of environmental contaminants on obesity.
Published: 2016

47. Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response

Author: Daniel Tomé, Martin Beaumont, Luciana Oquendo Pereira Lancha, Robert Benamouzig, Jean-Marc Blouin, Marta Grauso, Anne-Marie Davila, Nadezda Khodorova, François Blachier, Marc Audebert, Mireille Andriamihaja, Pierre-Henri Benetti, Frédéric Bouillaud, Annaïg Lan, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), University of São Paulo (USP), Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Fondation ARC pour la Recherche sur le cancer [20131200283], PRES Sorbonne Paris Cite, INRA, AgroParisTech, European Project: 613979,EC:FP7:KBBE,FP7-KBBE-2013-7-single-stage,MYNEWGUT(2013), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, 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 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), Université de Toulouse (UT)-Université de Toulouse (UT), Universidade de São Paulo = University of São Paulo (USP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne
Subjects: 0301 basic medicine, Sulfide, Colon, DNA damage, Hydrogen sulfide, [SDV]Life Sciences [q-bio], Nitric Oxide Synthase Type II, Sulfides, Mitochondrion, Biology, Biochemistry, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, Oxygen Consumption, Physiology (medical), Gene expression, Animals, Intestine, Large, Amino Acids, chemistry.chemical_classification, Inflammation, Interleukin-6, Microbiota, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular biology, Gastrointestinal Microbiome, Rats, Mitochondria, Nitric oxide synthase, 030104 developmental biology, Gene Expression Regulation, chemistry, Colonocyte, Fermentation, biology.protein, ETHE1, High-protein diet, Genotoxicity, Energy Metabolism, DNA Damage
Abstract: WOS:000371219400015; International audience; Protein fermentation by the gut microbiota releases in the large intestine lumen various amino-acid derived metabolites. Among them, hydrogen sulfide (H2S) in excess has been suspected to be detrimental for colonic epithelium energy metabolism and DNA integrity. The first objective of this study was to evaluate in rats the epithelial response to an increased exposure to H2S. Experiments from colonocyte incubation and intra-colonic instillation indicate that low millimolar concentrations of the sulfide donor NaHS reversibly inhibited colonocyte mitochondrial oxygen consumption and increased gene expression of hypoxia inducible factor 1 alpha (Hif-1 alpha) together with inflammation-related genes namely inducible nitric oxide synthase (iNos) and interleukin-6 (Il-6). Additionally, rat colonocyte H2S detoxification capacity was severely impaired in the presence of nitric oxide. Based on the gamma H(2)AX ICW technique, NaHS did not induce DNA damage in colonocytes. Since H2S is notably produced by the gut microbiota from sulfur containing amino acids, the second objective of the study was to investigate the effects of a high protein diet (HPD) on large intestine luminal sulfide content and on the expression of genes involved in H2S detoxification in colonocytes. We found that HPD markedly increased H2S content in the large intestine but the concomitant increase of the content mass maintained the luminal sulfide concentration. HPD also provoked an increase of sulfide quinone reductase (Sqr) gene expression in colonocytes, indicating an adaptive response to increased H2S bacterial production. In conclusion, low millimolar NaHS concentration severely affects colonocyte respiration in association with increased expression of genes associated with intestinal inflammation. Although HPD increases the sulfide content of the large intestine, the colonic adaptive responses to this modification limit the epithelial exposure to this deleterious bacterial metabolite. (C) 2016 Elsevier Inc. All rights reserved.
Published: 2016

48. Bisphenol A exposure disrupts neurotransmitters through modulation of transaminase activity in the brain of rodents

Author: Ana M. Soto, Nicolas J. Cabaton, Marie Tremblay-Franco, Daniel Zalko, Fabien Jourdan, Cécile Canlet, Métabolisme et Xénobiotiques (ToxAlim-MeX), 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), Tufts University School of Medicine, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-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)-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, Tufts University School of Medicine [Boston], Centre Cavaillès, La République des savoirs : Lettres, Sciences, Philosophie, Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Département de Philosophie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Département de Philosophie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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)-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: 0301 basic medicine, endocrine system, medicine.medical_specialty, bisphenol A, [SDV]Life Sciences [q-bio], Rodentia, Biology, Neurotransmission, Inhibitory postsynaptic potential, gamma-Aminobutyric acid, Transaminase, Postnatal day, 03 medical and health sciences, chemistry.chemical_compound, body weight, GABA, 0302 clinical medicine, Endocrinology, Phenols, Internal medicine, medicine, Animals, Humans, Benzhydryl compounds, MICE, BPA, NMR, nuclear magnetic resonance, PND, Benzhydryl Compounds, Transaminases, ComputingMilieux_MISCELLANEOUS, Neurotransmitter Agents, Perinatal Exposure, Brain, 030104 developmental biology, chemistry, Gestation, GABAergic, 030217 neurology & neurosurgery, medicine.drug
Abstract: An increasing body of literature suggests that perinatal exposure to low doses of bisphenol A (BPA) has lasting effects on brain development and/or behavior in rodents (1, 2). Concerns about the occurrence of similar effects in humans are based on the parallel increase of neurobehavioral conditions in humans that appear in rodents exposed to BPA (3), and on epidemiological studies (4). In their recent article, Franssen et al (5) demonstrated opposite dose-dependent effects of BPA on the neuroendocrine maturation of female rats exposed during early life from postnatal day (PND)1 to PND15. In animals exposed to a 0.025g BPA/kg bw (body weight)/d dose, neuroendocrine maturation related to puberty was found to be delayed, with opposite effects observed in animals exposed to a 5000g BPA/kg bw/d dose. Modulation of inhibitory -aminobutiric acid (GABA)ergic neurotransmission was found to be associated with the delayed maturation of GnRH secretion through increased GABAergic tone for the 0.025g BPA/kg bw/d dose; opposite effects were observed for the higher dose. These new findings prompted us to reexamine in more detail our results obtained for male mice exposed to very low doses of BPA from gestational day 8 to PND16 (maternal exposure to 0-, 0.025-, 0.25-, or 25g BPA/kg bw/d) (6). In this 2013 study, we used untargeted H-nuclear magnetic resonance (NMR) metabolomics to explore the metabolites present in a set of tissues, including male brains at PND21. All brain metabolites were included in a partial least square-discriminant analysis model, which demonstrated extremely significant differences between the 4 groups. GABA was one of the major metabolites responsible for intergroup differences. To better understand the mechanisms by which BPA disrupts brain development, we reanalyzed our raw data from 2013 with the purpose of 1) challenging the hypotheses by Franssen et al, and 2) seeking additional hypotheses that could explain the disruption of GABAergic pathways. We addressed the former by means of a 2 by 2 group comparison and the latter by analyzing the genome-scale metabolic net
Published: 2016

49. Special Issue « ECOTOX, the INRA's network of ecotoxicologists »

Author: Christian Mougin, Agnès Bouchez, Laurence Denaix, Francois Laurent, Fabrice Martin, ProdInra, Archive Ouverte, Ecologie fonctionnelle et écotoxicologie des agroécosystèmes ( ECOSYS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Université Paris-Saclay, Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques ( CARRTEL ), Institut National de la Recherche Agronomique ( INRA ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ), Interactions Sol Plante Atmosphère ( ISPA ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine ( Bordeaux Sciences Agro ), ToxAlim ( ToxAlim ), Institut National Polytechnique [Toulouse] ( INP ) -Institut National de la Recherche Agronomique ( INRA ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -Ecole Nationale Vétérinaire de Toulouse, Agroécologie [Dijon], Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté ( UBFC ), Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques (CARRTEL), Institut National de la Recherche Agronomique (INRA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Interactions Sol Plante Atmosphère (UMR ISPA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro), Métabolisme et Xénobiotiques (ToxAlim-MeX), 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 National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut National de la Recherche Agronomique (INRA), Interactions Sol Plante Atmosphère (ISPA), and Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: [SDV] Life Sciences [q-bio], [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: Special Issue « ECOTOX, the INRA's network of ecotoxicologists »
Published: 2016

50. Report on the fifth meeting of INRA’s national network of ecotoxicologists, ECOTOX

Author: Agnès Bouchez, Christian Mougin, Fabrice Martin-Laurent, Michel Mench, François Laurent, Laurence Denaix, Isabelle Lamy, Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques (CARRTEL), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut National de la Recherche Agronomique (INRA), Interactions Sol Plante Atmosphère (ISPA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro), 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), Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Biodiversité, Gènes et Communautés, Institut National de la Recherche Agronomique (INRA), Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Interactions Sol Plante Atmosphère (UMR ISPA), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Biodiversité, Gènes & Communautés (BioGeCo), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB), Ecologie fonctionnelle et écotoxicologie des agroécosystèmes ( ECOSYS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques ( CARRTEL ), Institut National de la Recherche Agronomique ( INRA ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ), Interactions Sol Plante Atmosphère ( ISPA ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine ( Bordeaux Sciences Agro ), ToxAlim ( ToxAlim ), Institut National Polytechnique [Toulouse] ( INP ) -Institut National de la Recherche Agronomique ( INRA ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -Ecole Nationale Vétérinaire de Toulouse, Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Institut National de la Recherche Agronomique ( INRA )
Subjects: [ SDV ] Life Sciences [q-bio], business.industry, Ecology, Health, Toxicology and Mutagenesis, Aquatic ecosystem, soils contaminants, [SDV]Life Sciences [q-bio], Environmental resource management, terrestrial ecosystems, General Medicine, Pollution, ecotoxicology, Geography, network, Environmental Chemistry, National Policy, Ecotoxicology, Ecosystem, Terrestrial ecosystem, fate impact, business, aquatic ecosystems
Abstract: The fifth meeting of INRA’s national network of ecotoxicologists took place on 25 to 27 November 2014 in Biarritz, France. The main aim of the meeting was to bring together ecotoxicologists from INRA and associated partners, providing them ample opportunity to share and discuss their latest scientific results as well as the national policy of research in ecotoxicology and to precise perspectives for the network.
Published: 2016

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