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2. The fate of mitochondria during platelet activation

Author

Grichine, Alexei, Jacob, Shancy, Eckly, Anita, Villaret, Joran, Joubert, Clotilde, Appaix, Florence, Pezet, Mylène, Ribba, Anne-Sophie, Denarier, Eric, Mazzega, Jacques, Rinckel, Jean-Yves, Lafanechère, Laurence, Elena-Herrmann, Bénédicte, Rowley, Jesse W., and Sadoul, Karin

Published
2023
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4. Multi-Method Quantification of Acetyl-Coenzyme A and Further Acyl-Coenzyme A Species in Normal and Ischemic Rat Liver

Author

Tokarska-Schlattner, Malgorzata, primary, Zeaiter, Nour, additional, Cunin, Valérie, additional, Attia, Stéphane, additional, Meunier, Cécile, additional, Kay, Laurence, additional, Achouri, Amel, additional, Hiriart-Bryant, Edwige, additional, Couturier, Karine, additional, Tellier, Cindy, additional, El Harras, Abderrafek, additional, Elena-Herrmann, Bénédicte, additional, Khochbin, Saadi, additional, Le Gouellec, Audrey, additional, and Schlattner, Uwe, additional

Published
2023
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8. Glycolysis-Mediated Changes in Acetyl-CoA and Histone Acetylation Control the Early Differentiation of Embryonic Stem Cells

Author

Moussaieff, Arieh, Rouleau, Matthieu, Kitsberg, Daniel, Cohen, Merav, Levy, Gahl, Barasch, Dinorah, Nemirovski, Alina, Shen-Orr, Shai, Laevsky, Ilana, Amit, Michal, Bomze, David, Elena-Herrmann, Bénédicte, Scherf, Tali, Nissim-Rafinia, Malka, Kempa, Stefan, Itskovitz-Eldor, Joseph, Meshorer, Eran, Aberdam, Daniel, and Nahmias, Yaakov

Published
2015
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11. Identification of Modulators of the C. elegans Aryl Hydrocarbon Receptor and Characterization of Transcriptomic and Metabolic AhR-1 Profiles

Author

Larigot, Lucie, primary, Bui, Linh-Chi, additional, de Bouvier, Marine, additional, Pierre, Ophélie, additional, Pinon, Grégory, additional, Fiocca, Justine, additional, Ozeir, Mohammad, additional, Tourette, Cendrine, additional, Ottolenghi, Chris, additional, Imbeaud, Sandrine, additional, Pontoizeau, Clément, additional, Blaise, Benjamin J., additional, Chevallier, Aline, additional, Tomkiewicz, Céline, additional, Legrand, Béatrice, additional, Elena-Herrmann, Bénédicte, additional, Néri, Christian, additional, Brinkmann, Vanessa, additional, Nioche, Pierre, additional, Barouki, Robert, additional, Ventura, Natascia, additional, Dairou, Julien, additional, and Coumoul, Xavier, additional

Published
2022
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14. A statistical framework to model the meeting-in-the-middle principle using metabolomic data: application to hepatocellular carcinoma in the EPIC study

Author

Assi, Nada, Fages, Anne, Vineis, Paolo, Chadeau-Hyam, Marc, Stepien, Magdalena, Duarte-Salles, Talita, Byrnes, Graham, Boumaza, Houda, Knüppel, Sven, Kühn, Tilman, Palli, Domenico, Bamia, Christina, Boshuizen, Hendriek, Bonet, Catalina, Overvad, Kim, Johansson, Mattias, Travis, Ruth, Gunter, Marc J., Lund, Eiliv, Dossus, Laure, Elena-Herrmann, Bénédicte, Riboli, Elio, Jenab, Mazda, Viallon, Vivian, and Ferrari, Pietro

Published
2015
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16. sj-docx-1-ict-10.1177_1534735420977666 – Supplemental material for Effects of an Exercise and Nutritional Intervention on Circulating Biomarkers and Metabolomic Profiling During Adjuvant Treatment for Localized Breast Cancer: Results From the PASAPAS Feasibility Randomized Controlled Trial

Author

Febvey-Combes, Olivia, Jobard, Elodie, Rossary, Adrien, Pialoux, Vincent, Aude-Marie Foucaut, Morelle, Magali, Delrieu, Lidia, Martin, Agnès, Caldefie-Chézet, Florence, Touillaud, Marina, Berthouze, Sophie E., Boumaza, Houda, Elena-Herrmann, Bénédicte, Bachmann, Patrick, Trédan, Olivier, Marie-Paule Vasson, and Fervers, Béatrice

Subjects
111708 Health and Community Services, FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110306 Endocrinology, 111299 Oncology and Carcinogenesis not elsewhere classified
Abstract

Supplemental material, sj-docx-1-ict-10.1177_1534735420977666 for Effects of an Exercise and Nutritional Intervention on Circulating Biomarkers and Metabolomic Profiling During Adjuvant Treatment for Localized Breast Cancer: Results From the PASAPAS Feasibility Randomized Controlled Trial by Olivia Febvey-Combes, Elodie Jobard, Adrien Rossary, Vincent Pialoux, Aude-Marie Foucaut, Magali Morelle, Lidia Delrieu, Agnès Martin, Florence Caldefie-Chézet, Marina Touillaud, Sophie E. Berthouze, Houda Boumaza, Bénédicte Elena-Herrmann, Patrick Bachmann, Olivier Trédan, Marie-Paule Vasson and Béatrice Fervers in Integrative Cancer Therapies

Published
2021
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17. Effects of an Exercise and Nutritional Intervention on Circulating Biomarkers and Metabolomic Profiling During Adjuvant Treatment for Localized Breast Cancer: Results From the PASAPAS Feasibility Randomized Controlled Trial

Author

Febvey-Combes, Olivia, primary, Jobard, Elodie, additional, Rossary, Adrien, additional, Pialoux, Vincent, additional, Foucaut, Aude-Marie, additional, Morelle, Magali, additional, Delrieu, Lidia, additional, Martin, Agnès, additional, Caldefie-Chézet, Florence, additional, Touillaud, Marina, additional, Berthouze, Sophie E., additional, Boumaza, Houda, additional, Elena-Herrmann, Bénédicte, additional, Bachmann, Patrick, additional, Trédan, Olivier, additional, Vasson, Marie-Paule, additional, and Fervers, Béatrice, additional

Published
2021
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18. Metabolomic Approaches to Study Chemical Exposure-Related Metabolism Alterations in Mammalian Cell Cultures

Author

Balcerczyk, Aneta, Damblon, Christian, Elena-Herrmann, Bénédicte, Panthu, Baptiste, Rautureau, Gilles J P, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), 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), Centre de RMN à très hauts champs de Lyon (CRMN), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Francophone Diabetes Society (SFD) ENS de Lyon, 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), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Magnetic Resonance Spectroscopy, [SDV]Life Sciences [q-bio], Cell Culture Techniques, Review, exposome, endometabolome, metabolomics, cell cultures, NMR, Mass Spectrometry, Culture Media, Xenobiotics, lcsh:Chemistry, exometabolome, lcsh:Biology (General), lcsh:QD1-999, Metabolome, Animals, Humans, lcsh:QH301-705.5
Abstract

International audience; Biological organisms are constantly exposed to an immense repertoire of molecules that cover environmental or food-derived molecules and drugs, triggering a continuous flow of stimuli-dependent adaptations. The diversity of these chemicals as well as their concentrations contribute to the multiplicity of induced effects, including activation, stimulation, or inhibition of physiological processes and toxicity. Metabolism, as the foremost phenotype and manifestation of life, has proven to be immensely sensitive and highly adaptive to chemical stimuli. Therefore, studying the effect of endo- or xenobiotics over cellular metabolism delivers valuable knowledge to apprehend potential cellular activity of individual molecules and evaluate their acute or chronic benefits and toxicity. The development of modern metabolomics technologies such as mass spectrometry or nuclear magnetic resonance spectroscopy now offers unprecedented solutions for the rapid and efficient determination of metabolic profiles of cells and more complex biological systems. Combined with the availability of well-established cell culture techniques, these analytical methods appear perfectly suited to determine the biological activity and estimate the positive and negative effects of chemicals in a variety of cell types and models, even at hardly detectable concentrations. Metabolic phenotypes can be estimated from studying intracellular metabolites at homeostasis in vivo, while in vitro cell cultures provide additional access to metabolites exchanged with growth media. This article discusses analytical solutions available for metabolic phenotyping of cell culture metabolism as well as the general metabolomics workflow suitable for testing the biological activity of molecular compounds. We emphasize how metabolic profiling of cell supernatants and intracellular extracts can deliver valuable and complementary insights for evaluating the effects of xenobiotics on cellular metabolism. We note that the concepts and methods discussed primarily for xenobiotics exposure are widely applicable to drug testing in general, including endobiotics that cover active metabolites, nutrients, peptides and proteins, cytokines, hormones, vitamins, etc.

Published
2020

19. General Guidelines for Sample Preparation Strategies in HR-$\mu$MAS NMR-based Metabolomics of Microscopic Specimens

Author

Lucas-Torres, Covadonga, Bernard, Thierry, Huber, Gaspard, Berthault, Patrick, Nishiyama, Yusuke, Kandiyal, Pancham, Elena-Herrmann, Bénédicte, Molin, Laurent, Solari, Florence, Bouzier-Sore, Anne-Karine, Wong, Alan, Laboratoire Structure et Dynamique par Résonance Magnétique (LCF) (LSDRM), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), JEOL, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), ANR-16-CE11-0023,HRmicroMAS,SPECTROSCOPIE RMN MICROSCOPIC SPECIMENS(2016), ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
microscopic samples, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, sample preparation, [CHIM.MATE]Chemical Sciences/Material chemistry, metabolomics, high-resolution magic angle spinning, NMR
Abstract

International audience; The study of the metabolome within tissues, organisms, cells or biofluids can be carried out by several bioanalytical techniques. Among them, nuclear magnetic resonance (NMR) is one of the principal spectroscopic methods. This is due to a sample rotation technique, high-resolution magic angle spinning (HR-MAS), which targets the analysis of heterogeneous specimens with a bulk sample mass from 5 to 10 mg. Recently, a new approach, high-resolution micro-magic angle spinning (HR-$\mu$MAS), has been introduced. It opens, for the first time, the possibility of investigating microscopic specimens (

Published
2020

20. General Guidelines for Sample Preparation Strategies in HR-µMAS NMR-based Metabolomics of Microscopic Specimens

Author

Lucas-Torres, Covadonga, Bernard, Thierry, Huber, Gaspard, Berthault, Patrick, Nishiyama, Yusuke, Kandiyal, Pancham S., Elena-Herrmann, Bénédicte, Molin, Laurent, Solari, Florence, Bouzier-Sore, Anne-Karine, and Wong, Alan

Subjects
microscopic samples, sample preparation, lcsh:QR1-502, metabolomics, Article, high-resolution magic angle spinning, lcsh:Microbiology, nmr
Abstract

The study of the metabolome within tissues, organisms, cells or biofluids can be carried out by several bioanalytical techniques. Among them, nuclear magnetic resonance (NMR) is one of the principal spectroscopic methods. This is due to a sample rotation technique, high-resolution magic angle spinning (HR-MAS), which targets the analysis of heterogeneous specimens with a bulk sample mass from 5 to 10 mg. Recently, a new approach, high-resolution micro-magic angle spinning (HR-μMAS), has been introduced. It opens, for the first time, the possibility of investigating microscopic specimens (

Published
2020

24. Metabolomic Profiling of Body Fluids in Mouse Models Demonstrates that Nuclear Magnetic Resonance Is a Putative Diagnostic Tool for the Presence of Thyroid Hormone Receptor α1 Mutations

Author

Zekri, Yanis, Nicolaisen, Trine, Klein, Anders, Dmytriyeva, Oksana, Lund, Jens, Ingerslev, Lars, Fritzen, Andreas, Carl, Christian, Lundsgaard, Anne-Marie, Frost, Mikkel, Ma, Tao, Schjerling, Peter, Gerhart-Hines, Zachary, Larsen, Steen, Richter, Erik, Kiens, Bente, Clemmensen, Christoffer, Lundsgaard, Anne‐Marie, Gerhart‐Hines, Zachary, Warnich, L., Dietzsch, E., Heyns, D.A., Nicholson, D.L., Retief, A.E., Holbech, Henrik, Matthiessen, Peter, Hansen, Martin, Schüürmann, Gerrit, Knapen, Dries, Reuver, Marieke, Sachs, Laurent, Kloas, Werner, Hilscherova, Klara, Leonard, Marc, Arning, Jürgen, Strauss, Volker, Iguchi, Taisen, Baumann, Lisa, Richard, Sabine, Guyot, Romain, Rey-Millet, Martin, Prieux, Margaux, Aubert, Denise, BOUMAZA, Houda, Markossian, Suzy, Busi, Baptiste, Rautureau, Gilles, Gauthier, Karine, Elena-Herrmann, Bénédicte, Flamant, Frederic, Rautureau, Gilles J.P., Institut de Génomique Fonctionnelle de Lyon (IGFL), 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), Centre de RMN à très hauts champs de Lyon (CRMN), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), French National Research Agency (ANR)ANR-15-CE14-0011-04 ThyroMUT2, Centre Européen de Résonance Magnétique Nucléaire à Très Hauts Champs (CERMNTHC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Reproduction et développement des plantes (RDP), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut des Sciences Analytiques (ISA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB ), Centre Hospitalier Universitaire [Grenoble] (CHU)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre Hospitalier Universitaire [Grenoble] (CHU), Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [2016-2019] (IAB [2016-2019]), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Male, Magnetic Resonance Spectroscopy, endocrine system diseases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], diagnostic, resistance to thyroid hormone α, integrated approach to testing and assessment, Récepteurs nucléaires, test guideline, MESH: Hypothyroidism, MESH: Body Fluids, Mice, 0302 clinical medicine, Endocrinology, Nuclear receptors, energy expenditure, energy metabolism, Régénération, MESH: Genes, erbA, MESH: Animals, hypothalamus, MESH: Metabolomics, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Genes, erbA, Thyroid, thyroid hormone disruption, thermogenesis, endocrine disruption, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, metabolomics, 3. Good health, Body Fluids, adverse outcome pathway, medicine.anatomical_structure, 030220 oncology & carcinogenesis, OECD, cross-species extrapolation, Thyroid Hormone Receptors alpha, endocrine system, MESH: Mutation, Thyroid Hormone Receptor Alpha-1, MESH: Thyroid Hormone Receptors alpha, Alpha (ethology), rare disease, 030209 endocrinology & metabolism, Biology, Hormone thyroïdienne, Key terms: Metabolomics, MESH: Workflow, 03 medical and health sciences, Metabolomics, Hypothyroidism, Developmental Neuroscience, MESH: Mice, Inbred C57BL, Biofluids, medicine, Animals, Humans, Regeneration, mouse models, skeletal muscle, Gene, AOP, MESH: Mice, browning, thyroid hormones, Thyroid hormone receptor, MESH: Humans, MESH: Magnetic Resonance Spectroscopy, biomarkers, thyroid hormone receptor, brown adipose tissue, thyroid hormone, MESH: Male, Mice, Inbred C57BL, nuclear magnetic resonance, Metabolomic profiling, resistance to thyroid hormone alpha, Mutation, Cancer research, IATA, Molecular Neuroscience, Hormone, Neuroscience
Abstract

International audience; Background: Resistance to thyroid hormone alpha (RTH alpha) is a rare genetic disease due to mutations in the THRA gene, which encodes thyroid hormone receptor alpha 1 (TR alpha 1). Since its first description in 2012, 46 cases of RTH alpha have been reported worldwide, corresponding to 26 different mutations of TR alpha 1. RTH alpha patients share some common symptoms with hypothyroid patients, without significant reduction in thyroid hormone level. The high variability of clinical features and the absence of reliable biochemical markers make the diagnosis of this disease difficult. Some of these mutations have been recently modeled in mice. Methods: In our study, we used four different mouse models heterozygous for frameshift mutations in the Thra gene. Two of them are very close to human mutations, while the two others have not yet been found in patients. We characterized the metabolic phenotypes of urine and plasma samples collected from these four animal models using an untargeted nuclear magnetic resonance (NMR)-based metabolomic approach. Results: Multivariate statistical analysis of the metabolomic profiles shows that biofluids of mice that carry human-like mutations can be discriminated from controls. Metabolic signatures associated with Thra mutations in urine and plasma are stable over time and clearly differ from the metabolic fingerprint of hypothyroidism in the mouse. Conclusion: Our results provide a proof-of-principle that easily accessible NMR-based metabolic fingerprints of biofluids could be used to diagnose RTH alpha in humans.

Published
2019

25. Metabolic Phenotyping of Adipose-Derived Stem Cells Reveals a Unique Signature and Intrinsic Differences between Fat Pads

Author

Lefevre, Camille, Panthu, Baptiste, Naville, Danielle, Guibert, Sylvie, Pinteur, Claudie, Elena-Herrmann, Bénédicte, Vidal, Hubert, Rautureau, Gilles J. P., Mey, Anne, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Chambre Régionale d'Agriculture des Pays de la Loire, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), INRA (Institut National de la Recherche Agronomique), CIRAD (Centre de Cooperation Internationale en Recherche Agronomique pour le Developpement): Glofoods programme, INSERM, Université Claude Bernard Lyon 1, INRA, INSERM [U1060-INRA 1397], and French Ministry of Higher Education and Scientific Research

Subjects
lcsh:Internal medicine, metabolic phenotyping, adipose derived stem cell, fat pads, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Article Subject, [SDV]Life Sciences [q-bio], hemic and immune systems, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], lcsh:RC31-1245, tissues, Research Article
Abstract

White adipose tissues are functionally heterogeneous and differently manage the excess of energy supply. While the expansion of subcutaneous adipose tissues (SAT) is protective in obesity, that of visceral adipose tissues (VAT) correlates with the emergence of metabolic diseases. Maintained in fat pads throughout life, adipose stem cells (ASC) are mesenchymal-like stem cells with adipogenesis and multipotent differentiation potential. ASC from distinct fat pads have long been reported to present distinct proliferation and differentiation potentials that are maintained in culture, yet the origins of these intrinsic differences are still unknown. Metabolism is central to stem cell fate decision in line with environmental changes. In this study, we performed high-resolution nuclear magnetic resonance (NMR) metabolomic analyses of ASC culture supernatants in order to characterize their metabolic phenotype in culture. We identified and quantified 29 ASC exometabolites and evaluated their consumption or secretion over 72 h of cell culture. Both ASC used glycolysis and mitochondrial metabolism, as evidenced by the high secretions of lactate and citrate, respectively, but V-ASC mostly used glycolysis. By varying the composition of the cell culture medium, we showed that glutaminolysis, rather than glycolysis, supported the secretion of pyruvate, alanine, and citrate, evidencing a peculiar metabolism in ASC cells. The comparison of the two types of ASC in glutamine-free culture conditions also revealed the role of glutaminolysis in the limitation of pyruvate routing towards the lactate synthesis, in S-ASC but not in V-ASC. Altogether, our results suggest a difference between depots in the capacity of ASC mitochondria to assimilate pyruvate, with probable consequences on their differentiation potential in pathways requiring an increased mitochondrial activity. These results highlight a pivotal role of metabolic mechanisms in the discrimination between ASC and provide new perspectives in the understanding of their functional differences.

Published
2019

26. Glucokinase sensitizes hepatocarcinoma cells to the lipogenic activity of fructose and controls accumulation of lipid droplets and secretion of triglyceride-rich lipoproteins

Author

Diaz, Olivier, Jacquemin, Clémence, Panthu, Baptiste, Elena-Herrmann, Bénédicte, Rautureau, Gilles, André, Patrice, Lotteau, Vincent, Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Contrôle traductionnel des ARNm eucaryotes et viraux – Translational control of Eukaryotic and Viral RNAs, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de RMN à très hauts champs de Lyon (CRMN), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)

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

International audience

Published
2019

27. Structure elucidation of a complex CO2-based organic framework material by NMR crystallography† †Electronic supplementary information (ESI) available: Experimental procedures, spectra, modelled data and structures. See DOI: 10.1039/c5sc03810c

Author

Leclaire, Julien, Poisson, Guillaume, Ziarelli, Fabio, Pepe, Gerard, Fotiadu, Frédéric, Paruzzo, Federico M., Rossini, Aaron J., Dumez, Jean-Nicolas, Elena-Herrmann, Bénédicte, and Emsley, Lyndon

Subjects
Chemistry
Abstract

A three-dimensional structural model of a complex CO2-based organic framework made from high molecular weight, self-assembled, flexible and multi-functional oligomeric constituents has been determined de novo by solid-state NMR including DNP-enhanced experiments., A three-dimensional structural model of a complex CO2-based organic framework made from high molecular weight, self-assembled, flexible and multi-functional oligomeric constituents has been determined de novo by solid-state NMR including DNP-enhanced experiments. The complete assignment of the 15N, 13C and 1H resonances was obtained from a series of two-dimensional through space and through bond correlation experiments. MM-QM calculations were used to generate different model structures for the material which were then evaluated by comparing multiple experimental and calculated NMR parameters. Both NMR and powder X-ray diffraction were evaluated as tools to determine the packing by crystal modelling, and at the level of structural modelling used here PXRD was found not to be a useful complement. The structure determined reveals a highly optimised H-bonding network that explains the unusual selectivity of the self-assembly process which generates the material. The NMR crystallography approach used here should be applicable for the structure determination of other complex solid materials.

Published
2016

28. NMR Pulse Sequences for Metabolomics

Author

Elena-Herrmann, Bénédicte, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Hector C. Keun

Subjects
[CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

32. A Proton NMR Metabolomic Investigation of an Emerging Genetic Disease

Author

BOUMAZA, Houda, Markossian, Suzy, Rautureau, Gilles, Gauthier-Vanacker, Karine, Flamant, Frederic, Elena-Herrmann, Bénédicte, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), NMR Methods for Metabolism - Methodes RMN en métabolomique, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Resistance to thyroid hormones, biomark- ers, diagnosis, [CHIM]Chemical Sciences, Multivariate statistical analysis, RTHα, metabolomics, NMR
Abstract

https://smmap2017.sciencesconf.org/; International audience; Resistance to thyroid hormone (RTHα) due to mutations in the thyroid hormone receptor alpha (TRα1), which is encoded by the THRA gene, is a recently discovered genetic disease. Patients present a high variability in clinical features (skeletal dysplasia, growth retardation, intellectual disability, etc...), and the absence of reliable biochemical markers make the diagnosis of this disease difficult. Since its first description in 2012, 25 cases of RTHα have been reported worldwide, corresponding to 14 different mutations of TRα1. In this context, a 1H nuclear magnetic resonance (NMR) metabolomic study was initiated, among a range of other phenotyping studies (including skeletal, blood and heart phenotype, neurodevelopment), to evaluate the impact of different mutations of TRα1 on the metabolism, and pos- sibly identify biomarkers contributing to RTHα diagnostic in humans.Considering that the mouse Thra and human THRA genes display extensive sequence similarities, mouse lines with Thra mutations are highly relevant animal models for RTHα. We used CRISPR/Cas9 genome editing to introduce 5 different germline mutations in the mouse Thra gene: 4 frameshift and 1 missense mutation closely modeling the mutations found in RTHα patients. Urine and plasma samples from adult mice carrying these Thra mutations were analyzed by NMR with associated wild-type controls. Multi- variate statistical analysis (OPLS-DA models) shows that samples collected from specific groups of mice carrying frameshift mutations can be discriminated from control samples collected from wild-type lit- termates, while mutations associated with minor phenotypic changes do not discriminate from controls. Our results reveal the presence of metabotype changes induced by Thra mutations, which provides a proof-of-principle that NMR metabolomics can be used to diagnose RTHα.

Published
2017

33. Method for the differentiation of Escherichia Coli and Shigella bacteria by means of NMR spectrometry

Author

Canard, Isabelle, Elena-Herrmann, Bénédicte, Mirande, Caroline, Palama, Tony, Rautureau, Gilles, Sprugnoli, Claude, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Bussy, Agnès

Subjects
[CHIM.ANAL] Chemical Sciences/Analytical chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry
Abstract

The invention relates to a method for the proton NMR spectrometry-based differentiation of Escherichia colibacteria and Shigella bacteria, said method comprising the steps of: obtaining at least one supernatant of at least one suspension of bacteria that could be Escherichia coli or Shigella; preparing at least one sample suitable for proton NMR spectrometry analysis, by mixing at least one fraction of at least one supernatant with a deuterated buffer; obtaining at least one NMR spectrum of the at least one sample; analysing the peaks of the at least one spectrum corresponding to the following metabolites: acetate, alanine, aspartate, ethanol, lactose, lysine, Na-acetyllysine, propionate, serine, succinate, threonine and valine; determining if it is Escherichia coli or Shigella bacteria., La présente invention concerne un procédé de différenciation par spectrométrie RMN u proton entre une bactérie Escherichia coli et une bactérie Shigella, ledit procédé omportant les étapes consistant à : - Obtenir au moins un surnageant d'au moins une suspension de bactéries susceptibles d'être Escherichia coli ou Shigella; - Préparer au moins un échantillon adapté à une analyse en spectrométrie RMN du proton, par mélange d'au moins une fraction du au moins un surnageant avec un tampon deutéré; - Obtenir au moins un spectre RMN du moins un échantillon, - Analyser les pics dudit au moins un spectre correspondant aux métabolites suivant : acétate, alanine, aspartate, éthanol, lactose, lysine, Na-acétyllysine, propionate, sérine, succinate, thréonine et valine; - Déterminer s'il s'agit d'une bactérie Escherichia coli ou Shigella.

Published
2016

34. A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

Author

Jobard, Elodie, Trédan, Olivier, Postoly, Déborah, André, Fabrice, Martin, Anne-Laure, Elena-Herrmann, Bénédicte, Boyault, Sandrine, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Dept Rech Translat & Innovat, Centre Léon Bérard [Lyon], Dept Med Oncol, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), R&D UNICANCER, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCL/UNICANCER), UNICANCER-UNICANCER, The grants received in support of this research work are Agence Nationale de la Recherche (ANR) grants: ANR-10-INBS-01-01 and ANR-10-COHO-04, CANTO consortium. This project was initiated by Gilles Thomas (Centre Leon Berard, Lyon, France)., and ANR-10-COHO-0004,CANTO,Etude des toxicités chroniques des traitements anticancéreux chez les patientes porteuses cancer(2010)

Subjects
Serum, Blood Specimen Collection, Magnetic Resonance Spectroscopy, Article, lcsh:Chemistry, nuclear magnetic resonance, Plasma, lcsh:Biology (General), lcsh:QD1-999, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, pre-analytics, [CHIM]Chemical Sciences, Humans, Metabolomics, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], quality control, lcsh:QH301-705.5
Abstract

International audience; The recent thriving development of biobanks and associated high-throughput phenotyping studies requires the elaboration of large-scale approaches for monitoring biological sample quality and compliance with standard protocols. We present a metabolomic investigation of human blood samples that delineates pitfalls and guidelines for the collection, storage and handling procedures for serum and plasma. A series of eight pre-processing technical parameters is systematically investigated along variable ranges commonly encountered across clinical studies. While metabolic fingerprints, as assessed by nuclear magnetic resonance, are not significantly affected by altered centrifugation parameters or delays between sample pre-processing (blood centrifugation) and storage, our metabolomic investigation highlights that both the delay and storage temperature between blood draw and centrifugation are the primary parameters impacting serum and plasma metabolic profiles. Storing the blood drawn at 4 degrees C is shown to be a reliable routine to confine variability associated with idle time prior to sample pre-processing. Based on their fine sensitivity to pre-analytical parameters and protocol variations, metabolic fingerprints could be exploited as valuable ways to determine compliance with standard procedures and quality assessment of blood samples within large multi-omic clinical and translational cohort studies.

Published
2016

36. Metabolic Investigation of the Mycoplasmas from the Swine Respiratory Tract

Author

Ferrarini , Mariana G, Siqueira , Franciele Maboni, Mucha , Scheila G, Palama , Tony, Jobard , Elodie, Elena-Herrmann , Bénédicte, Vasconcelos , Ana Tereza Ribeiro, Tardy , Florence, Schrank , Irene S, Zaha , A, Sagot , Marie-France, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centro de Biotecnologia [Porto Alegre] (CBiot), Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] (LNCC / MCT), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Mycoplasmoses des Ruminants - UMR (MYCO), Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Centro de Biotecnologia [Porto Alegre] ( CBiot ), Universidade Federal do Rio Grande do Sul [Porto Alegre] ( UFRGS ), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale ( ERABLE ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), NMR Methods for Metabolism - Methodes RMN en métabolomique, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] ( LNCC / MCT ), VetAgro Sup ( VAS ), Mycoplasmoses des ruminants [Lyon], Université de Lyon-VetAgro Sup ( VAS ), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Mycoplasma, Mollicutes, Metabolic network, Metabolism, Whole-genome metabolic reconstruction, Hydrogen peroxide, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH : Mycoplasma
Abstract

International audience; BackgroundThe respiratory tract of swine is colonized by several bacteria among which are three Mycoplasma species: Mycoplasma flocculare, Mycoplasma hyopneumoniae and Mycoplasma hyorhinis. While colonization by M. flocculare is virtually asymptomatic, M. hyopneumoniae is the causative agent of enzootic pneumonia and M. hyorhinis is present in cases of pneumonia, polyserositis and arthritis. The genomic resemblance among these three Mycoplasma species combined with their different levels of pathogenicity is an indication that they have unknown mechanisms of virulence and differential expression, as for most mycoplasmas.MethodsIn this work, we performed whole-genome metabolic network reconstructions for these three mycoplasmas. Cultivation tests and metabolomic experiments through nuclear magnetic resonance spectroscopy (NMR) were also performed to acquire experimental data and further refine the models reconstructed in silico.ResultsEven though the refined models have similar metabolic capabilities, interesting differences include a wider range of carbohydrate uptake in M. hyorhinis, which in turn may also explain why this species is a widely contaminant in cell cultures. In addition, the myo-inositol catabolism is exclusive to M. hyopneumoniae and may be an important trait for virulence. However, the most important difference seems to be related to glycerol conversion to dihydroxyacetone-phosphate, which produces toxic hydrogen peroxide. This activity, missing only in M. flocculare, may be directly involved in cytotoxicity, as already described for two lung pathogenic mycoplasmas, namely Mycoplasma pneumoniae in human and Mycoplasma mycoides subsp. mycoides in ruminants. Metabolomic data suggest that even though these mycoplasmas are extremely similar in terms of genome and metabolism, distinct products and reaction rates may be the result of differential expression throughout the species.ConclusionsWe were able to infer from the reconstructed networks that the lack of pathogenicity of M. flocculare if compared to the highly pathogenic M. hyopneumoniae may be related to its incapacity to produce cytotoxic hydrogen peroxide. Moreover, the ability of M. hyorhinis to grow in diverse sites and even in different hosts may be a reflection of its enhanced and wider carbohydrate uptake. Altogether, the metabolic differences highlighted in silico and in vitro provide important insights to the different levels of pathogenicity observed in each of the studied species.

Published
2016

37. NMR investigation of targeted therapy effects on the host metabolism for HER-2 positive breast cancer

Author

Jobard, Elodie, Bachelot, Thomas, Campone, Mario, Trédan, Olivier, Elena-Herrmann, Bénédicte, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Dept Rech Translat & Innovat, Centre Léon Bérard [Lyon], Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Nucléaire, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), and RFMF - Réseau Francophone de Métabolomique et Fluxomique

Subjects
breast cancer, mTOR inhibitor, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, serum, RMN, targeted therapies
Abstract

International audience; Many advances in recent years, such as the use of targeted therapies, have enabled to improve the management of cancer patients. Understanding the effect of targeted therapies on the human metabolism is essential to predict the response to treatments and adjust personalized therapy. mTOR is an attractive target for cancer’s therapeutic intervention because of its key role in the regulation of protein translation, cell growth and metabolism. We present here a metabolomic investigation exploring the impact of mTOR inhibition on serum metabolic profiles from patients with non-metastatic breast cancer overexpressing HER-2. We detail the metabolic signatures associated with the response to an HER-2 inhibitor standard treatment (trastuzumab), or a combined HER-2 and mTOR (everolimus) inhibitors therapy. Pre-treatment, on-treatment and post-treatment serum samples were available for 79 patients with HER-2 positive breast cancer from the French multicentre, randomized phase II trial RADHER. Fasting patients were randomized between two treatments: trastuzumab (group A) and a trastuzumab and everolimus combination (experimental group B). For each patient, clinicopathological data were recorded. 340 serum metabolic profiles were obtained using 1H NMR spectroscopy (800MHz). Statistical multivariate methods were exploited to build models for sample classification and extract group-specific metabolic signatures. ANOVA analysis and multiple testing corrections of the p-values were used to derive statistically significant associations of individual metabolites. The longitudinal series of serum samples available for each patient was exploited to investigate the effect of the combination B on the patient’s metabolism over time and to compare it with the standard reference treatment A. For each arm, serum metabolic profiles are compared before, over and after treatment. Similarly, the fingerprints are compared between treatments. Clear and significant O-PLS discrimination is observed only for the arm B between metabolic profiles at baseline and after one week of treatment (N: 57, R2Y = 0.404, Q2 = 0.199), after four weeks of treatment (N: 54, R2Y = 0.603, Q2 = 0.301), one week after the end of treatment (N: 53, R2Y = 0.734, Q2 = 0.569), three weeks after the end of treatment (N =51, R2Y = 0.767, Q2 = 0.493). The trastuzumab and everolimus combination causes faster changes in patient metabolism than standard treatment and a residual effect is also observed several weeks after ending of the treatment (up to 3 weeks). Analysis of metabolic fingerprints highlights the involvement of several metabolic pathways reflecting a systemic effect, particularly on the liver and visceral fat. Furthermore, comparison of the metabolic profiles between the two arms (either four or seven weeks after the beginning of the treatment) shows that everolimus, an mTOR inhibitor, is responsible for the host metabolism modification observed in the experimental arm

Published
2016

38. Evolution of urine metabolomic profiles in newborns

Author

Scalabre, Aurélien, Jobard, Elodie, Gaillard, Ségolène, Elena-Herrmann, Bénédicte, Mure, Pierre-Yves, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), and RFMF - Réseau Francophone de Métabolomique et Fluxomique

Subjects
newborns, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, urine, NMR, metabolomic
Abstract

International audience; Metabolomics provides untargeted identification of all detectable low molecular-weight molecules by profiling without a priori the metabolic signatures of biological samples in connection to pathophysiological events. The goal of metabolomic studies is to identify relevant biomarkers or composite metabolic patterns associated with particular disease status. Urine is particularly suited for metabolomic analysis in newborns and children, due to its simple and non-invasive method of collection. Its biochemical composition is correlated to a number of factors such as genotype, gender, disease, nutritional state and age. The number of metabolomic studies in pediatrics is rising, but little is known concerning age-related changes in urine metabolic profiles and newborn metabolic maturation over time. The aim of this study was to investigate changes in urine metabolic profiles during the first four months of life using 1H-nuclear magneticresonance (NMR) spectroscopy combined with multivariate statistical analysis. Urine samples were collected from 91 newborns under 4 months old without nephrologic or urologic disease. The mean age was 68 days ± 24. The1H-NMR spectra were analyzed using Principal Component Analysis (PCA) and the effect of age on the urinary metabolite profile was observed even from this unsupervised analysis. Further analysis using Orthogonal Partial Least Squares (OPLS) methodology was performed and a model with good predictive power was calculated, allowing the identification of an age-related metabolic profile. We observed the most significant evolution between 2 and 3 months of life. Our results allow a deeper understanding of newborn metabolic maturation. They contribute to identifying potential confounding factors in the application of metabolomics in newborns.

Published
2016

39. Métabolomics

Author

Elena-Herrmann, Bénédicte, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
[CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

42. Longitudinal serum metabolomics evaluation of trastuzumab and everolimus combination as pre-operative treatment for HER-2 positive breast cancer patients

Author

Jobard, Elodie, primary, Trédan, Olivier, additional, Bachelot, Thomas, additional, Vigneron, Arnaud M., additional, Aït-Oukhatar, Céline Mahier, additional, Arnedos, Monica, additional, Rios, Maria, additional, Bonneterre, Jacques, additional, Diéras, Véronique, additional, Jimenez, Marta, additional, Merlin, Jean-Louis, additional, Campone, Mario, additional, and Elena-Herrmann, Bénédicte, additional

Published
2017
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43. A serum metabolomic fingerprint of bevacizumab and temsirolimus combination as first-line treatment of metastatic renal cell carcinoma.

Author

Jobard, Elodie, Blanc, Ellen, Négrier, Sylvie, Escudier, Bernard, Gravis, Gwenaelle, Chevreau, Christine, Elena-Herrmann, Bénédicte, Trédan, Olivier, Négrier, Sylvie, Elena-Herrmann, Bénédicte, and Trédan, Olivier

Subjects
ANTINEOPLASTIC agents, PROTEIN metabolism, NEOVASCULARIZATION inhibitors, HETEROCYCLIC compounds, INDOLE compounds, KIDNEY tumors, METABOLISM, RENAL cell carcinoma, SERUM, THERAPEUTICS, RAPAMYCIN
Abstract

Background: Renal cell carcinoma is one of the most chemoresistant cancers, and its metastatic form requires administration of targeted therapies based on angiogenesis or mTOR inhibitors. Understanding how these treatments impact the human metabolism is essential to predict the host response and adjust personalised therapies. We present a metabolomic investigation of serum samples from patients with metastatic RCC (mRCC) to identify metabolic signatures associated with targeted therapies.Methods: Pre-treatment and serial on-treatment sera were available for 121 patients participating in the French clinical trial TORAVA, in which 171 randomised patients with mRCC received a bevacizumab and temsirolimus combination (experimental arm A) or a standard treatment: either sunitinib (B) or interferon-α+bevacizumab (C). Metabolic profiles were obtained using nuclear magnetic resonance spectroscopy and compared on-treatment or between treatments.Results: Multivariate statistical modelling discriminates serum profiles before and after several weeks of treatment for arms A and C. The combination A causes faster changes in patient metabolism than treatment C, detectable after only 2 weeks of treatment. Metabolites related to the discrimination include lipids and carbohydrates, consistently with the known RCC metabolism and side effects of the drugs involved. Comparison of the metabolic profiles for the three arms shows that temsirolimus, an mTOR inhibitor, is responsible for the faster host metabolism modification observed in the experimental arm.Conclusions: In mRCC, metabolomics shows a faster host metabolism modification induced by a mTOR inhibitor as compared with standard treatments. These results should be confirmed in larger cohorts and other cancer types. [ABSTRACT FROM AUTHOR]

Published
2015
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45. Insights on the virulence of swine respiratory tract mycoplasmas through genome-scale metabolic modeling

Author

Ferrarini, Mariana G., primary, Siqueira, Franciele M., additional, Mucha, Scheila G., additional, Palama, Tony L., additional, Jobard, Élodie, additional, Elena-Herrmann, Bénédicte, additional, R. Vasconcelos, Ana T., additional, Tardy, Florence, additional, Schrank, Irene S., additional, Zaha, Arnaldo, additional, and Sagot, Marie-France, additional

Published
2016
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46. HCV infection reprograms the hepatic glucose and glutamine metabolism

Author

Lévy, Pierre, Michelet, M., Brault, C., Sallé, A., Parent, Romain, Durantel, David, Elena-Herrmann, Bénédicte, Steffen, H.-M., Zoulim, Fabien, Bartosch, Birke, Odenthal, M., Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe 15, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Equipee 16, Centre de RMN à très hauts champs, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institute for Pathology, University Hospital Cologne, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Hospices Civils de Lyon ( HCL ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), ISA - Centre de RMN à très hauts champs, Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)

Subjects
[CHIM.ANAL]Chemical Sciences/Analytical chemistry, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry
Abstract

communication par affiche; International audience; Background and Aims: Hepatitis C virus (HCV) is the only virus that is known to perturb hepatic glucose and lipid metabolism with important patho-physiological consequences. Chronic carriers often develop steatosis, insulin resistance and type 2 diabetes, which resolve with successful antiviral treatment. Therefore it is thought that HCV interferes directly with the lipogenic and glycolytic pathways and requires these changes for its replication. However, the exact circumstances of this metabolic reprogramming still remain vague and require further analysis. Here we investigate some fundamental changes in glucose and glutamine metabolism linked to HCV infection. Methods: RNA derived from Huh7.5 cells infected or not with JFH1 and from biopsies of chronic HCV patients were used for RT-qPCR analysis with primers targeting metabolic genes. Nutrient deprivation and biochemical and NMR-based metabolic flux analysis were performed with JFH1 infected Huh7.5 cell culture extracts. Results: We show that HCV modulates the transcript levels of some key regulators of glucose metabolism (HIF-1 a, PKM2, G6PD) in the hepatocyte-derived cell-line Huh7.5 as well as liver biopsies of patients with chronic hepatitis C, which hinted at changes to glycolytic fluxes. In addition, we found enzymes and factorsregulating glutamine metabolism (MYC, SLC1A5, SLC7A5, GLS) to be upregulated by HCV. Indeed, cell proliferation rates of HCV infected and uninfected cells in conditioned growth media showed that infected cells become dependent on glutamine and lose their glucose dependence. NMR-based metabolomic assays further corroborated these findings. We then showed that silencing of MYC, an oncogene and metabolic transcription factor known to induce glutamine addiction, as well as silencing of GLS, considerably reduced HCV infection. Conclusions: Altogether, these data suggest that HCV reprograms the hepatocyte metabolism and establishes glutamine dependence. This HCV-induced metabolic reprogramming is similar to that commonly found in many types of tumor cells. Because these changes seem to be required for viral replication, we are currently investigating their roles in the various steps of the viral life cycle, and their impact on the pathological features associated with chronic hepatitis C.

Published
2013

47. A NMR metabonomic approach to explore early biomarkers of hepatocellular carcinoma in the european prospective investigation into cancer and nutrition (EPIC)

Author

Fages, Anne, Ferrari, Pietro, Pontoizeau, Clément, Fedirko, Veronika, Elena-Herrmann, Bénédicte, Jenab, Mazda, Duarte-Salles, T., Bussy, Agnès, ISA - Centre de RMN à très hauts champs, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and International Agency for Cancer Research (IACR)

Subjects
[CHIM.ANAL] Chemical Sciences/Analytical chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry
Abstract

communication par affiche; Primary liver cancer (PLC; ranked sixth in incidence and third in mortality worldwide) is a cancer grouping composed of hepatocellular (HCC) and intrahepatic bile duct carcinomas. HCC make up the bulk of PLC and are highly malignant, usually diagnosed at late stages and often have very poor prognosis with limited treatment options. Thus, there is a need to identify early diagnostic biomarkers of HCC risk. Also, it is plausible that metabolic imbalances, reflective of obesity, diabetes, and lifestyle habits play a central role in HCC etiology. Thus, a NMR metabonomic study was undertaken in a case-control study nested within EPIC, a large prospective cohort of over 520,000 subjects from 23 centers in 10 Western European countries. Detailed dietary/lifestyle data and biological samples (stored under liquid nitrogen) were collected at enrolment from the majority of participants. After an average of 7.6 years of follow-up, 112 first primary incident HCC cases were identified and matched to control subjects (1:2; by age, sex, study centre). Serum samples from matched cases and controls were analyzed by high-field 1H NMR spectroscopy with the following objectives: (i) to identify early predictive biomarkers of HCC by following a metabonomic approach and (ii) to identify metabolomic profiles representative of distinct dietary or lifestyle patterns. Although the protocols of the EPIC study were not specifically designed with metabolomic analyses in mind, extensive pilot testing has shown that EPIC serum samples are suitable for this type of analysis. High-resolution one-dimensional 1 H NMR (NOESY and CPMG) spectral profiles were recorded at 800MHz. Additional 2D 1H-1H (Jres, TOCSY) and 1H-13C (HSQC) data were recorded for metabolite assignments. We present here the first results of the metabonomic analysis of the EPIC HCC nested case-control study that enabled the identification of a metabolomic profile discriminating cases from controls based on serum collected prior to diagnosis. The potential of this study to identify both pre-diagnostic biomarkers as well as those related to exposures associated with disease risk, may have relevant public health impact and enhance understanding of HCC cancer aetiology, particularly in HCC cases arising in the absence of hepatitis B or C infections.

Published
2013

48. La métabolomique par RMN et ses applications en biologie végétale, toxicologie et médecine

Author

Canlet, Cécile, Shintu, Laetitia, Elena-Herrmann, Bénédicte, xénobiotiques, 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 des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), ISA - Centre de RMN à très hauts champs, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Centre de RMN à très hauts champs, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Bussy, Agnès, 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), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[CHIM.ANAL] Chemical Sciences/Analytical chemistry, biofluids, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, biostatistics, chemometrics, metabolomics, NMR, metabolites
Abstract

National audience; Cet article présente les principes ainsi que les outils analytiques et chimiométriques qui sont au cœur du développement des approches d'analyse métabolomique par RMN. Il en illustre les applications variées au travers d'exemples choisis dans différents domaines de la biologie et de la médecine, concernant l'étude des organismes génétiquement modifiés, les interactions plantes/environnement, la toxicologie environnementale, la pharmacologie, la cancérologie ou l'épidémiologie moléculaire.

Published
2012

49. High-resolution NMR metabonomics: revealing metabolic fingerprints from whole organisms to biofluids

Author

Elena-Herrmann, Bénédicte, ISA - Centre de RMN à très hauts champs, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and Bussy, Agnès

Subjects
[CHIM.ANAL] Chemical Sciences/Analytical chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2011

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