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11 results on '"MESH: Endotoxemia"'

1. H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation

Author

Tiphaine M. N. Camarasa, Catherine Fitting, Melanie Hamon, Jean-Marc Cavaillon, Orhan Rasid, Christine Chevalier, Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris], Cytokines et Inflammation, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Work in the M.A.H. laboratory received financial support from Institut Pasteur and the French National Research Agency (ANR-EPIBACTIN). O.R. was supported by a stipend from the Pasteur – Paris University International PhD Program for part of this work. T.M.-N.C. is supported by a fellowship from the Foundation for Medical Research (Mariane Josso Prize)., We would like to thank Olivier Dussurget and Emmanuel Lemichez for the kind gift of the luminescent E. coli, Thomas Kohler and Sven Hammerschmidt for the S. pneumoniae strain, and Ignacio Santecchia for technical assistance with E. coli culture., ANR-17-CE12-0007,EpiBactIn,Modifications epigenomiques induites par l'interaction hote-bacteries(2017), and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, MESH: Inflammation, Male, Adoptive cell transfer, Histone methyltransferase activity, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Stimulation, NK cells, Systemic inflammation, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, sepsis, Histones, Mice, 0302 clinical medicine, MESH: Animals, lcsh:QH301-705.5, Escherichia coli Infections, MESH: Histones, biology, MESH: Escherichia coli, NK cell memory, Cell biology, Killer Cells, Natural, Histone, Enhancer Elements, Genetic, MESH: Immunologic Memory, MESH: Immunity, Innate, medicine.symptom, epigenetic, MESH: Killer Cells, Natural, MESH: Interferon-gamma, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Interferon-gamma, medicine, Escherichia coli, Animals, Epigenetics, MESH: Mice, MESH: Escherichia coli Infections, Inflammation, Innate immune system, H3K4me1, Immunotherapy, MESH: Male, Endotoxemia, Immunity, Innate, 030104 developmental biology, lcsh:Biology (General), MESH: Endotoxemia, biology.protein, MESH: Enhancer Elements, Genetic, Immunologic Memory, 030217 neurology & neurosurgery
Abstract

Summary: Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mice, NK cells acquire cell-intrinsic memory-like properties, showing increased production of IFNγ upon specific secondary stimulation. The NK cell memory response is detectable for at least 9 weeks and contributes to protection from E. coli infection upon adoptive transfer. Importantly, we reveal a mechanism essential for NK cell memory, whereby an H3K4me1-marked latent enhancer is uncovered at the ifng locus. Chemical inhibition of histone methyltransferase activity erases the enhancer and abolishes NK cell memory. Thus, NK cell memory develops after endotoxemia in a histone methylation-dependent manner, ensuring a heightened response to secondary stimulation. : Rasid et al. show that sepsis-like systemic inflammation induces a type of long-lasting innate immune memory in NK cells, which can protect from E. coli infection. This is achieved by revealing an enhancer of IFNγ through histone monomethylation. Keywords: NK cells, NK cell memory, sepsis, epigenetic, H3K4me1

Published
2019

2. Lactobacillus rhamnosus GG and Oat Beta‐Glucan Regulated Fatty Acid Profiles along the Gut‐Liver‐Brain Axis of Mice Fed with High Fat Diet and Demonstrated Antioxidant and Anti‐Inflammatory Potentials

Author

Jean-Marie Galano, Hani El-Nezami, Zuzanna Maria Kundi, Jetty Chung-Yung Lee, Thierry Durand, Yu Fung Yau, The University of Hong Kong (HKU), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Lipopolysaccharides, Male, Lactobacillus rhamnosus GG, Isoprostane, Antioxidant, beta-Glucans, Avena, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: Dietary Supplements, isoprostane, MESH: Eating, Antioxidants, Cecum, chemistry.chemical_compound, Eating, Non-alcoholic Fatty Liver Disease, oat beta-glucan, MESH: Avena, MESH: Animals, Food science, 2. Zero hunger, chemistry.chemical_classification, biology, MESH: beta-Glucans, Lacticaseibacillus rhamnosus, Anti-Inflammatory Agents, Non-Steroidal, Brain, food and beverages, MESH: Anti-Inflammatory Agents, Non-Steroidal, medicine.anatomical_structure, Liver, fatty acid metabolism, lipids (amino acids, peptides, and proteins), MESH: Caco-2 Cells, Biotechnology, Polyunsaturated fatty acid, animal structures, Diet, High-Fat, hydroxyeicosatetraenoic acid, 03 medical and health sciences, MESH: Brain, Lactobacillus rhamnosus, MESH: Mice, Inbred C57BL, medicine, otorhinolaryngologic diseases, Animals, Humans, MESH: Fatty Acids, Volatile, 030109 nutrition & dietetics, MESH: Humans, Fatty acid metabolism, MESH: Non-alcoholic Fatty Liver Disease, Prebiotic, Probiotics, fungi, MESH: Antioxidants, Fatty acid, biology.organism_classification, Fatty Acids, Volatile, MESH: Lactobacillus rhamnosus, Endotoxemia, MESH: Male, Mice, Inbred C57BL, MESH: Diet, High-Fat, 030104 developmental biology, chemistry, MESH: Endotoxemia, Dietary Supplements, Caco-2 Cells, MESH: Lipopolysaccharides, MESH: Probiotics, Food Science, MESH: Liver
Abstract

International audience; Scope: This study takes a novel approach to investigate the anti-inflammatory and antioxidant effects of prebiotic oat beta-glucan (OAT) and the probiotic Lactobacillus rhamnosus GG (LGG) against high-fat diets (HFD) by examining the fatty acid profiles in the gut-liver-brain axis.Method and results: HFD-fed C57BL/6N mice are supplemented with OAT and/or LGG for 17 weeks. Thereafter, mass spectrometry-based targeted lipidomics is employed to quantify short-chain fatty acids (SCFA), polyunsaturated fatty acids (PUFA), and oxidized PUFA products in the tissues. Acetate levels are suppressed by HFD in all tissues but reversed in the brain and liver by supplementation with LGG, OAT, or LGG + OAT, and in cecum content by LGG. The n-6/n-3 polyunsaturated fatty acid (PUFA) ratio is elevated by HFD in all tissues but is lowered by LGG and OAT in the cecum and the brain, and by LGG + OAT in the brain, suggesting the anti-inflammatory property of LGG and OAT. LGG and OAT synergistically, but not individually attenuate the increase in non-enzymatic oxidized products, indicating their synbiotic antioxidant property.Conclusion: The regulation of the fatty acid profiles by LGG and OAT, although incomplete, but demonstrates their anti-inflammatory and antioxidant potentials in the gut-liver-brain axis against HFD.

Published
2020

3. Immune Cell Toll-like Receptor 4 Mediates the Development of Obesity- and Endotoxemia-Associated Adipose Tissue Fibrosis

Author

Jacques Grober, Vladimir Stich, Philippe Gui, Corinne Lefort, Geneviève Tavernier, Virginie Bourlier, Isabelle K. Vila, Lenka Rossmeislová, Lucile Mir, Katie Louche, Anne Bouloumié, Nathalie Viguerie, Pierre Marie Badin, Balbine Roussel, Alexia Zakaroff-Girard, Dominique Langin, Cedric Moro, Marie Adeline Marques, Laurent Monbrun, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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, Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), PHOTONIQUE (XLIM-PHOTONIQUE), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Forschungsinstitut für Rationalisierung e.V. (FIR) an der RWTH Aachen, Franco-czech Laboratory for clinical research on obesity, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), I.K.V. was supported by fellowships from Inserm and Région Midi-Pyrénées. This work was supported by grants from Agence Nationale de la Recherche (LIPOB and OBELIP projects), Région Midi-Pyrénées, Fondation pour la Recherche Médicale, and the Commission of the European Communities (projects DIABAT, HEPADIP, and ADAPT) (to D.L.) and by a grant from Société Francophone du Diabète (to C.M.)., Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Departament Geodinàmica i Geofísica, Facultat de Geologia, Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Charles University [Prague], Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Hôpital de Rangueil-Institut National de la Santé et de la Recherche Médicale ( INSERM ), PHOTONIQUE ( XLIM-PHOTONIQUE ), XLIM ( XLIM ), Université de Limoges ( UNILIM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Limoges ( UNILIM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), U858 Institut de médecine moléculaire de Rangueil (I2MR), and Institut National de la Santé et de la Recherche Médicale

Subjects
Lipopolysaccharides, MESH: Signal Transduction, MESH: Inflammation, MESH : Toll-Like Receptor 4, Adipose tissue, MESH : Adipocytes, MESH : Lipopolysaccharides, Mice, chemistry.chemical_compound, Fibrosis, Adipocyte, Adipocytes, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Obesity, MESH: Animals, lcsh:QH301-705.5, Mice, Inbred C3H, Toll-like receptor, MESH : Diet, High-Fat, MESH: Toll-Like Receptor 4, 3. Good health, MESH: Insulin Resistance, Adipose Tissue, MESH: Fibrosis, MESH : Fibrosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Obesity, MESH : Insulin Resistance, MESH: Adipose Tissue, Signal Transduction, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adipose tissue macrophages, Biology, Diet, High-Fat, MESH : Adipose Tissue, General Biochemistry, Genetics and Molecular Biology, Immune system, MESH : Mice, Inbred C3H, Internal medicine, MESH : Mice, medicine, Animals, Humans, Obesity, MESH: Mice, Inbred C3H, MESH: Mice, MESH: Adipocytes, Inflammation, MESH : Signal Transduction, MESH : Inflammation, MESH: Humans, MESH : Endotoxemia, MESH : Humans, 3T3-L1, medicine.disease, MESH : Disease Models, Animal, Endotoxemia, Toll-Like Receptor 4, Disease Models, Animal, MESH: Diet, High-Fat, Endocrinology, lcsh:Biology (General), chemistry, MESH: Endotoxemia, MESH : Animals, Insulin Resistance, MESH: Disease Models, Animal, MESH: Lipopolysaccharides, Adipocyte hypertrophy
Abstract

International audience; Adipose tissue fibrosis development blocks adipocyte hypertrophy and favors ectopic lipid accumulation. Here, we show that adipose tissue fibrosis is associated with obesity and insulin resistance in humans and mice. Kinetic studies in C3H mice fed a high-fat diet show activation of macrophages and progression of fibrosis along with adipocyte metabolic dysfunction and death. Adipose tissue fibrosis is attenuated by macrophage depletion. Impairment of Toll-like receptor 4 signaling protects mice from obesity-induced fibrosis. The presence of a functional Toll-like receptor 4 on adipose tissue hematopoietic cells is necessary for the initiation of adipose tissue fibrosis. Continuous low-dose infusion of the Toll-like receptor 4 ligand, lipopolysaccharide, promotes adipose tissue fibrosis. Ex vivo, lipopolysaccharide-mediated induction of fibrosis is prevented by antibodies against the profibrotic factor TGFβ1. Together, these results indicate that obesity and endotoxemia favor the development of adipose tissue fibrosis, a condition associated with insulin resistance, through immune cell Toll-like receptor 4.

Published
2014

4. Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice

Author

Rémy Burcelin, Claude Knauf, Nathalie M. Delzenne, Rodrigo Bibiloni, Audrey M. Neyrinck, Patrice D. Cani, Aurélie Waget, Simon, Marie Francoise, Unit of Pharmacokinetics, Metabolism, Nutrition, and Toxicology (PMNT-73/69), Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Nutrition and Health, Nestlé Research Center | Centre de recherche Nestlé [Lausanne], Nestlé S.A.-Nestlé S.A., Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), and Nestlé Research Center

Subjects
Male, MESH: Inflammation, MESH: Bifidobacterium, Lipopolysaccharide, Endocrinology, Diabetes and Metabolism, Mice, Obese, Adipose tissue, Type 2 diabetes, MESH: Bacteroides, MESH: Base Sequence, Gut flora, medicine.disease_cause, MESH: Genotype, Feces, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Diabetes Mellitus, Experimental, Bacteroides, MESH: Obesity, MESH: Animals, Cecum, MESH: Mice, Obese, 2. Zero hunger, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, MESH: Feces, MESH: Crosses, Genetic, Anti-Bacterial Agents, 3. Good health, RNA, Bacterial, Female, medicine.symptom, MESH: RNA, Bacterial, medicine.medical_specialty, Genotype, 030209 endocrinology & metabolism, Inflammation, Biology, digestive system, Diabetes Mellitus, Experimental, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Anti-Bacterial Agents, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Animals, Obesity, MESH: Mice, Crosses, Genetic, 030304 developmental biology, Intestinal permeability, Base Sequence, MESH: Cecum, medicine.disease, biology.organism_classification, Endotoxemia, MESH: Male, Mice, Inbred C57BL, Lactobacillus, Endocrinology, chemistry, MESH: Endotoxemia, Immunology, Bifidobacterium, MESH: Female, MESH: Lactobacillus, Oxidative stress
Abstract

OBJECTIVE—Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases. RESEARCH DESIGN AND METHODS—We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect. RESULTS—We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat–fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14−/− mutant mice mimicked the metabolic and inflammatory effects of antibiotics. CONCLUSIONS—This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.

Published
2008

5. Emulsified lipids increase endotoxemia: possible role in early postprandial low-grade inflammation

Author

Laugerette, Fabienne, Vors, Cécile, Géloën, Alain, Chauvin, Marie-Agnès, Soulage, Christophe, Lambert-Porcheron, Stéphanie, Peretti, Noël, Alligier, Maud, Burcelin, Rémy, Laville, Martine, Vidal, Hubert, Michalski, Marie-Caroline, Régulations métaboliques, nutrition et diabètes (RMND), 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Multidisciplinaire de Biochimie des Lipides (IMBL), Covalab-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-07-PNRA-0007,FLORINFLAM,Effets modulateurs de fibres alimentaires sur la flore bactérienne et l'inflammation pour la prévention des maladies métaboliques induites par un régime gras.(2007), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), and Agence Nationale de la Recherche under reference ANR-07-PNRA-007-01 (FLORINFLAM project).,Agence Nationale de la Recherche under reference ANR-07-PNRA-007-01 (FLORINFLAM project).

Subjects
MESH: Emulsions, MESH: Inflammation, endotoxin, MESH: Rats, MESH: Intestinal Absorption, MESH: Random Allocation, digestion, emulsion, MESH: Atherosclerosis, lipid, MESH: Endotoxins, MESH: Animals, MESH: Receptors, Immunologic, MESH: Humans, MESH: Antigens, CD14, digestive, oral, and skin physiology, MESH: Adult, MESH: Rats, Wistar, MESH: Interleukin-6, MESH: Male, MESH: Chylomicrons, nutrition, inflammation, MESH: Young Adult, MESH: Dietary Fats, MESH: Endotoxemia, MESH: Postprandial Period, lipids (amino acids, peptides, and proteins), MESH: Caco-2 Cells, MESH: Lipopolysaccharides, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Low-grade inflammation is a risk factor for the onset of atherosclerosis. Little is known about the involvement of endotoxin absorption from the gut during the digestion of lipids. In the present study, we first investigated in humans the impact of a mixed meal containing dispersed lipids on postprandial endotoxemia and inflammation. We then investigated the effect of (i) oil emulsification in vivo in rats and (ii) fatty acid amounts in vitro using Caco-2 cells on postprandial endotoxemia. In humans, postprandial endotoxemia increased early after the meal. Moreover, we evidenced that the endotoxin receptor sCD14 increased during digestion and that chylomicrons could contribute to absorbed endotoxin transport. This could explain the significant peak of inflammatory cytokine IL-6 that we observed 2 h after the mixed meal. Interestingly, in rats, the emulsion led to both higher endotoxemia and hypertriglyceridemia than oil and compared to a control saline load. In vitro, incubation of Caco-2 cells with increasing fatty acid concentrations enhanced epithelial absorption of endotoxin. To our knowledge, this is the first study evidencing in healthy humans that, following a mixed meal containing lipids, increased endotoxemia is associated with raised sCD14 and a peak of IL-6. On a repeated basis, this may thus be a triggering cascade for the onset of atherosclerosis. In this respect, optimizing both dietary fat amount and structure could be a possible strategy to limit such low-grade endotoxemia and inflammation by the control of postprandial lipemia.

Published
2011

6. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation

Author

Marie-Caroline Michalski, Cécile Vors, Noël Peretti, Fabienne Laugerette, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), 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)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Fabienne Laugerette acknowledges grants from Institut Benjamin Delessert and Société Française de Nutrition. Cécile Vors is a recipient of doctoral grand from INRA & CNIEL. Marie-Caroline Michalski acknowledges a grant from ALFEDIAM., Institut National de la Recherche Agronomique (INRA)-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), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Vericel, Evelyne, 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)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
MESH: Inflammation, Metabolic inflammation, 030309 nutrition & dietetics, Endogeny, MESH: Metabolic Diseases, Biochemistry, Mice, MESH: Endotoxins, MESH: Obesity, MESH: Animals, Intestinal Mucosa, Subclinical infection, MESH: Lipid Metabolism, 0303 health sciences, General Medicine, 3. Good health, Intestines, MESH: Insulin Resistance, MESH: Dietary Fats, lipids (amino acids, peptides, and proteins), medicine.symptom, Digestion, Lipid digestion, MESH: Intestines, medicine.medical_specialty, MESH: Rats, Inflammation, Biology, 03 medical and health sciences, Insulin resistance, Metabolic Diseases, Internal medicine, medicine, Animals, Humans, Obesity, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Metagenome, medicine.disease, Lipid Metabolism, Dietary Fats, Endotoxemia, Rats, Endotoxins, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, MESH: Endotoxemia, Metagenome, Insulin Resistance, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Metabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly during the digestion of lipids. The aim of the present review is to highlight recently gained knowledge regarding the links between high fat diets, lipid digestion, intestinal microbiota and metabolic endotoxemia & inflammation.

Published
2011

7. Emulsified lipids increase endotoxemia: possible role in early postprandial low-grade inflammation.: Lipids and endotoxemia

Author

Laugerette, Fabienne, Vors, Cécile, Géloën, Alain, Chauvin, Marie-Agnès, Soulage, Christophe, Lambert-Porcheron, Stéphanie, Peretti, Noël, Alligier, Maud, Burcelin, Rémy, Laville, Martine, Vidal, Hubert, Michalski, Marie-Caroline, Vericel, Evelyne, Alimentation et nutrition humaine - Effets modulateurs de fibres alimentaires sur la flore bactérienne et l'inflammation pour la prévention des maladies métaboliques induites par un régime gras. - - FLORINFLAM2007 - ANR-07-PNRA-0007 - PNRA - VALID, Régulations métaboliques, nutrition et diabètes (RMND), 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Multidisciplinaire de Biochimie des Lipides (IMBL), 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)-Centre National de la Recherche Scientifique (CNRS)-Covalab, Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ANR-07-PNRA-0007,FLORINFLAM,Effets modulateurs de fibres alimentaires sur la flore bactérienne et l'inflammation pour la prévention des maladies métaboliques induites par un régime gras.(2007)

Subjects
MESH: Emulsions, MESH: Inflammation, endotoxin, MESH: Rats, MESH: Intestinal Absorption, MESH: Random Allocation, digestion, emulsion, MESH: Atherosclerosis, lipid, MESH: Endotoxins, MESH: Animals, MESH: Receptors, Immunologic, MESH: Humans, MESH: Antigens, CD14, digestive, oral, and skin physiology, MESH: Adult, MESH: Rats, Wistar, MESH: Interleukin-6, MESH: Male, MESH: Chylomicrons, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, nutrition, inflammation, MESH: Young Adult, MESH: Dietary Fats, MESH: Endotoxemia, MESH: Postprandial Period, lipids (amino acids, peptides, and proteins), MESH: Caco-2 Cells, MESH: Lipopolysaccharides, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Low-grade inflammation is a risk factor for the onset of atherosclerosis. Little is known about the involvement of endotoxin absorption from the gut during the digestion of lipids. In the present study, we first investigated in humans the impact of a mixed meal containing dispersed lipids on postprandial endotoxemia and inflammation. We then investigated the effect of (i) oil emulsification in vivo in rats and (ii) fatty acid amounts in vitro using Caco-2 cells on postprandial endotoxemia. In humans, postprandial endotoxemia increased early after the meal. Moreover, we evidenced that the endotoxin receptor sCD14 increased during digestion and that chylomicrons could contribute to absorbed endotoxin transport. This could explain the significant peak of inflammatory cytokine IL-6 that we observed 2 h after the mixed meal. Interestingly, in rats, the emulsion led to both higher endotoxemia and hypertriglyceridemia than oil and compared to a control saline load. In vitro, incubation of Caco-2 cells with increasing fatty acid concentrations enhanced epithelial absorption of endotoxin. To our knowledge, this is the first study evidencing in healthy humans that, following a mixed meal containing lipids, increased endotoxemia is associated with raised sCD14 and a peak of IL-6. On a repeated basis, this may thus be a triggering cascade for the onset of atherosclerosis. In this respect, optimizing both dietary fat amount and structure could be a possible strategy to limit such low-grade endotoxemia and inflammation by the control of postprandial lipemia.

Published
2011

8. Late N-acetylcysteine treatment prevents the deficits induced in the offspring of dams exposed to an immune stress during gestation

Author

Rose Aimar, Tangui Maurice, Michel Vignes, Gilles Cambonie, Janique Guiramand, Fabien Lanté, Johann Meunier, Gérard Barbanel, Marie-Céleste de Jesus Ferreira, Catherine Cohen-Solal, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)

Subjects
Lipopolysaccharides, Male, MESH: Hippocampus, Long-Term Potentiation, alpha-Tocopherol, Drug Evaluation, Preclinical, Hippocampus, Water maze, MESH: Rats, Sprague-Dawley, Hippocampal formation, Antioxidants, Developmental psychology, Rats, Sprague-Dawley, Acetylcysteine, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, MESH: Animals, MESH: Maternal Exposure, MESH: Glutathione, 0303 health sciences, Long-term potentiation, MESH: Neuroprotective Agents, MESH: Memory Disorders, Glutathione, 3. Good health, Neuroprotective Agents, MESH: alpha-Tocopherol, Maternal Exposure, MESH: Pregnancy Complications, Prenatal Exposure Delayed Effects, MESH: Drug Evaluation, Preclinical, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.drug, medicine.medical_specialty, MESH: Rats, Offspring, Cognitive Neuroscience, MESH: Drug Administration Schedule, Drug Administration Schedule, MESH: Prenatal Exposure Delayed Effects, 03 medical and health sciences, MESH: Acetylcysteine, MESH: Long-Term Potentiation, Internal medicine, medicine, Animals, Maze Learning, 030304 developmental biology, Memory Disorders, Fetus, business.industry, MESH: Maze Learning, MESH: Antioxidants, Endotoxemia, MESH: Male, Rats, Pregnancy Complications, Endocrinology, MESH: Endotoxemia, Synaptic plasticity, MESH: Lipopolysaccharides, business, Neuroscience, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; Prenatal infection is a major stressful experience leading to enhanced susceptibility for mental illnesses in humans. We recently reported in rats, that oxidative stress and glutathione (GSH) shortage occurred in fetal male brain after lipopolysaccharide (LPS) to the dams and that these responses might be involved in the neurodevelopmental deficits observed in adolescent offspring. Furthermore, pretreatment with N-acetylcysteine (NAC) before LPS avoided both delayed synaptic plasticity and mnesic performance deficits. Since NAC is one of the few medications permitted in pregnant women, this study evaluated the ability of NAC to serve as a protective therapy even after the LPS challenge. Pregnant rats received a single ip injection of E. coli LPS, two days before delivery, and were given NAC in their tap water after the LPS. GSH was evaluated at the time of its expected drop in the hippocampus of male fetuses, whereas long-term potentiation (LTP) in the CA1 area of the hippocampus and spatial memory in the water-maze were recorded in 28-day-old male offspring. Post-treatment with NAC, four hours after the LPS challenge fully prevented the drop in the GSH hippocampal content. LTP, as well as spatial learning were completely protected. NAC administration at delivery also partially restored the LTP whereas post-treatment two days later was inefficient. Another set of dams were supplemented with alpha-tocopherol prior to LPS exposure, enhancing the alpha-tocopherol levels in fetal hippocampus. This treatment did not prevent the LPS-induced synaptic plasticity impairment. These results point to fetal hippocampal GSH as a major target of the detrimental effects of in utero LPS challenge. The therapeutic window of NAC extends up to birth, suggesting that this drug might be clinically useful even after an immuno-inflammatory episode.

Published
2008

9. Bactericidal and anti-endotoxic properties of short cationic peptides derived from a snake venom Lys49 phospholipase A2

Author

Steve Quiros, Edgardo Moreno, Carlos Santamaría, Jean-Pierre Gorvel, Bruno Lomonte, Javier Pizarro-Cerdá, Silda Larios, Faculdad de Microbiologia, Instituto Clodomiro Picado, Universidad Nacional de Costa Rica, Universidad Nacional Autónoma de Managua [Nicaragua], Institut Pasteur [Paris], Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Universidad Nacional [Heredia, Costa Rica], Institut Pasteur [Paris] (IP), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Lipopolysaccharides, Salmonella typhimurium, VENENOS DE SERPIENTES, Polymyxin, Venom, Peptide, Reptilian Proteins, MESH: Gram-Positive Bacteria, Myoblasts, Mice, Phospholipase A2, MESH: Endotoxins, MESH: Gram-Negative Bacteria, Pharmacology (medical), Bothrops, MESH: Animals, MESH: Peptide Fragments, chemistry.chemical_classification, biology, MESH: Neutralization Tests, SNAKE VENOMS, Infectious Diseases, Biochemistry, Snake venom, BACTERICIDES, MESH: Crotalid Venoms, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Phospholipases A, BACTERICIDAS, MESH: Peritonitis, medicine.drug_class, Myotoxin, Antimicrobial peptides, Neurotoxins, Myotoxin II, MESH: Bothrops, Peritonitis, Gram-Positive Bacteria, Group II Phospholipases A2, Phospholipases A, Microbiology, Cell Line, Neutralization Tests, Crotalid Venoms, Gram-Negative Bacteria, medicine, Animals, Humans, MESH: Myoblasts, MESH: Mice, MESH: Neurotoxins, Pharmacology, Phospholipase A, MESH: Humans, PEPTIDOS, Snake Venom, MESH: Salmonella typhimurium, Endotoxemia, Peptide Fragments, MESH: Cell Line, Endotoxins, Phospholipases A2, chemistry, Susceptibility, MESH: Endotoxemia, biology.protein, MESH: Lipopolysaccharides
Abstract

The activities of short synthetic, nonhemolytic peptides derived from the C-terminal region of myotoxin 11, a catalytically inactive phospholipase A(2) homologue present in the venom of the snake Bothrops asper, have been shown to reproduce the bactericidal activity of the parent protein. They combine cationic and hydrophobic-aromatic amino acids, thus functionally resembling the antimicrobial peptides of innate defenses. This study evaluated the antimicrobial and antiendotoxic properties of a 13-mer derivative peptide of the C-terminal sequence from positions 115 to 129 of myotoxin II, named pEM-2. This peptide (KKWRWWLKALAKK) showed bactericidal activity against both gram-positive and gram-negative bacteria. In comparison to previously described peptide variants derived from myotoxin II, the toxicity of pEM-2 toward eukaryotic cells in culture was significantly reduced, being similar to that of lactoferricin B but lower than that of polymyxin B. The all-D enantiomer of pEM-2 [pEM-2 (D)] retained the same bactericidal potency Of its L-enantiomeric counterpart, but it showed an enhanced ability to counteract the lethal activity of an intraperitoneal lipopolysaccharide challenge in mice, which correlated with a significant reduction of the serum tumor necrosis factor alpha levels triggered by this endotoxin. Lethality induced by intraperitoneall infection of mice with Eschelichia coli or Salmonella enterica serovar Typhimurium was reduced by the administration of pEM-2 (D). These results demonstrate that phospholipase A(2)-derived peptides may have the potential to counteract microbial infections and encourage further evaluations of their actions in vivo. Las actividades de péptidos sintéticos cortos, no hemolíticos, derivados de la región C-terminal de la miotoxina II, un homólogo de la fosfolipasa A2 catalíticamente inactivo presente en el veneno de la serpiente Bothrops asper, han han demostrado que reproducen la actividad bactericida de la proteína madre. Combinan aminoácidos catiónicos e hidrofóbicos-aromáticos, asemejándose así funcionalmente a los péptidos antimicrobianos de las defensas innatas. En este estudio evaluó las propiedades antimicrobianas y antiendotóxicas de un péptido derivado de 13 meros de la secuencia C-terminal C-terminal de las posiciones 115 a 129 de la miotoxina II, denominado pEM-2. Este péptido (KKWRWLKALAKK) mostró actividad bactericida contra bacterias tanto grampositivas como gramnegativas. En comparación con las variantes de péptidos péptido derivado de la miotoxina II, la toxicidad del pEM-2 para las células eucariotas en cultivo se redujo significativamente fue significativamente reducida, siendo similar a la de la lactoferricina B pero inferior a la de la polimixina B. El enantiómero todo-D de pEM-2 [pEM-2 (D)] conservó la misma potencia bactericida que su homólogo enantiomérico L pero mostró una mayor capacidad para contrarrestar la actividad letal de una provocación con lipopolisacárido intraperitoneal de lipopolisacárido intraperitoneal en ratones, lo que se correlaciona con una reducción significativa de los niveles séricos del factor de necrosis tumoral alfa desencadenados por esta endotoxina. La letalidad inducida por la infección intraperitoneal de ratones con Escherichia coli o Salmonella enterica serovar Typhimurium se redujo con la administración de pEM-2 (D). Estos resultados demuestran que los péptidos derivados de la fosfolipasa A2 pueden tener el potencial de contrarrestar las infecciones microbianas y y animan a seguir evaluando sus acciones in vivo. Universidad Nacional, Costa Rica Escuela de Medicina Veterinaria

Published
2005

10. HMR1402, a potassium ATP channel blocker during hyperdynamic porcine endotoxemia: effects on hepato-splanchnic oxygen exchange and metabolism

Author

Peter Radermacher, Damian Vassilev, Xavier Leverve, Uwe B. Brückner, Hendrik Bracht, Balázs Hauser, Gebhard Fröba, Antje Pittner, Pierre Asfar, Zsolt Iványi, Marek Nalos, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm - University Hospital of Ulm, Bioénergétique fondamentale et appliquée, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sektion Chirurgische Forschung, and Hamant, Sarah

Subjects
Male, endocrine system, Swine, Potassium, Hemodynamics, chemistry.chemical_element, Blood Pressure, MESH: Lactates, 030204 cardiovascular system & hematology, Pharmacology, Critical Care and Intensive Care Medicine, Oxygen, MESH: Thiourea, 03 medical and health sciences, 0302 clinical medicine, Oxygen Consumption, Intensive care, MESH: Potassium Channel Blockers, Potassium Channel Blockers, Medicine, Animals, Channel blocker, MESH: Animals, MESH: Oxygen Consumption, Pyruvates, MESH: Swine, MESH: Pyruvates, Splanchnic Circulation, business.industry, Thiourea, 030208 emergency & critical care medicine, Metabolism, MESH: Blood Pressure, Endotoxemia, MESH: Male, 3. Good health, chemistry, Liver, Anesthesia, MESH: Endotoxemia, Lactates, Female, Splanchnic, business, MESH: Female, MESH: Liver
Abstract

International audience; OBJECTIVE: To assess the effects of the potassium ATP (KATP) channel blocker HMR1402 (HMR) on systemic and hepato-splanchnic hemodynamics, oxygen exchange and metabolism during hyperdynamic porcine endotoxemia. DESIGN: Prospective, randomized, controlled study with repeated measures. SETTING. Animal laboratory. SUBJECTS: Eighteen pigs allocated to receive endotoxin alone (control group, CON, n=10) or endotoxin and HMR (6 mg/kg h(-1), n=8). INTERVENTIONS: Anesthetized, mechanically ventilated, and instrumented pigs receiving continuous i.v. endotoxin were resuscitated with hetastarch to maintain mean arterial pressure (MAP) >60 mmHg. Twelve hours after starting the endotoxin infusion, they received HMR or its vehicle for another 12 h. RESULTS: HMR transiently increased MAP by about 15 mmHg, but this effect was only present during the first 1 h of infusion. The HMR decreased cardiac output due to a fall in heart rate, and thereby reduced liver blood flow. While liver O(2) delivery and uptake remained unchanged, HMR induced hyperlactatemia [from 1.5 (1.1; 2.0), 1.4 (1.2; 1.8), and 1.2 (0.8; 2.0) to 3.1 (1.4; 3.2), 3.2 (1.6; 6.5), and 3.0 (1.0; 5.5) mmol/l in the arterial, portal and hepatic venous samples, respectively] and further increased arterial [from 8 (3; 13) to 23 (11; 57); p

Published
2004

11. Adenosine triphosphate-magnesium dichloride during hyperdynamic porcine endotoxemia: Effects on hepatosplanchnic oxygen exchange and metabolism

Author

Marek Nalos, Antje Pittner, Marc Theisen, Peter Radermacher, Uwe B. Brückner, G. Froeba, Pierre Asfar, Carole Ichai, Franz Ploner, Can Ince, Michael K. Georgieff, Xavier Leverve, Biomedical Engineering and Physics, Translational Physiology, Hamant, Sarah, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm - University Hospital of Ulm, Sektion Chirurgische Forschung, Bioénergétique fondamentale et appliquée, and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Cardiac output, MESH: Interleukin-10, Swine, Statistics as Topic, Hemodynamics, Vasodilation, MESH: Liver Circulation, Critical Care and Intensive Care Medicine, Adenosine Triphosphate, 0302 clinical medicine, MESH: Adenosine Triphosphate, MESH: Animals, Prospective Studies, Splanchnic Circulation, MESH: Oxygen Consumption, MESH: Swine, 0303 health sciences, MESH: Nitrites, Interleukin-10, 3. Good health, Liver, MESH: Models, Animal, MESH: Nitrates, Shock (circulatory), Anesthesia, Models, Animal, medicine.symptom, Splanchnic, MESH: Oxygen, Liver Circulation, inorganic chemicals, MESH: Hemodynamics, Mean arterial pressure, medicine.medical_specialty, 03 medical and health sciences, Oxygen Consumption, MESH: Splanchnic Circulation, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Nitrites, MESH: Statistics as Topic, 030304 developmental biology, Hetastarch, Nitrates, Tumor Necrosis Factor-alpha, business.industry, 030208 emergency & critical care medicine, Blood flow, Endotoxemia, MESH: Prospective Studies, Oxygen, Endocrinology, MESH: Tumor Necrosis Factor-alpha, MESH: Endotoxemia, business, MESH: Liver
Abstract

International audience; OBJECTIVE: To assess the effects of adenosine triphosphate-magnesium dichloride (ATP-MgCl2) on systemic and hepatosplanchnic hemodynamics, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic normotensive porcine endotoxemia. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Seventeen pigs were divided into two groups: eight animals receiving endotoxin served as a control group and nine animals received endotoxin (lipopolysaccharide) and ATP-MgCl2. INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented. Endotoxemia was achieved by continuous intravenous infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch targeted to maintain mean arterial pressure of >75 mm Hg. Twelve hours after the start of the endotoxin infusion, ATP-MgCl2, or its vehicle, were administered for 12 hrs. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure was maintained in the control group because of a sustained increase in cardiac output achieved by fluid resuscitation, whereas ATP-MgCl2 significantly decreased mean arterial pressure because of further systemic vasodilatation. ATP-MgCl2 markedly increased portal venous flow. In contrast to the controls, hepatic arterial flow remained unchanged until the end of the experiment, despite the further increase in cardiac output. The ileal mucosal-arterial PCO2 gap (Delta PCO2) progressively increased (p

Published
2002

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