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51. Docosahexaenoic acid, protectin synthesis: relevance against atherothrombogenesis

Author

Lagarde, Michel, Liu, Miao, Véricel, Evelyne, Calzada, Catherine, Chen, Ping, Driss, Fathi, Guichardant, Michel, 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), 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), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm, Ministry of Education and Research, ANR, and Carnot LISA institute., 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), and 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)

Subjects
Blood platelets, Leukocytes, lipids (amino acids, peptides, and proteins), Lipoxygenases, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Cyclooxygenases
Abstract

International audience; DHA is an abundant nutrient from marine lipids: its specific biological effects have been investigated in human volunteers, taking into consideration the dose effects. We report herein that, at dosages below 1 g/d, DHA proved to be effective in lowering blood platelet function and exhibited an 'antioxidant' effect. However, this was no longer the case following 1*6 g/d, showing then a U-shape response. The antioxidant effect has been observed in platelets as well as LDL, of which the redox status is assumed to be crucial in their relationship with atherosclerosis. Second, the oxygenated products of DHA, especially protectins produced by lipoxygenases, have been considered for their potential to affect blood platelets and leucocytes. It is concluded that DHA is an interesting nutrient to reduce atherothrombogenesis, possibly through complementary mechanisms involving lipoxygenase products of DHA.

Published
2013
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52. Skeletal muscle insulin resistance is induced by 4-hydroxy-2-hexenal, a by-product of <italic>n</italic>-3 fatty acid peroxidation.

Author

Soulage, Christophe O., Sardón Puig, Laura, Soulère, Laurent, Zarrouki, Bader, Guichardant, Michel, Lagarde, Michel, and Pillon, Nicolas J.

Abstract

Aims/hypothesis: Oxidative stress is involved in the pathophysiology of insulin resistance and its progression towards type 2 diabetes. The peroxidation of n-3 polyunsaturated fatty acids produces 4-hydroxy-2-hexenal (4-HHE), a lipid aldehyde with potent electrophilic properties able to interfere with many pathophysiological processes. The aim of the present study was to investigate the role of 4-HHE in the development of insulin resistance.Methods: 4-HHE concentration was measured in plasma from humans and rats by GC–MS. Insulin resistance was estimated in healthy rats after administration of 4-HHE using hyperinsulinaemic–euglycaemic clamps. In muscle cells, glucose uptake was measured using 2-deoxy-d-glucose and signalling pathways were investigated by western blotting. Intracellular glutathione was measured using a fluorimetric assay kit and boosted using 1,2-dithiole-3-thione (D3T).Results: Circulating levels of 4-HHE in type 2 diabetic humans and a rat model of diabetes (obese Zucker diabetic fatty rats), were twice those in their non-diabetic counterparts (33 vs 14 nmol/l, p < 0.001), and positively correlated with blood glucose levels. During hyperinsulinaemic–euglycaemic clamps in rats, acute intravenous injection of 4-HHE significantly altered whole-body insulin sensitivity and decreased glucose infusion rate (24.2 vs 9.9 mg kg−1 min−1, p < 0.001). In vitro, 4-HHE impaired insulin-stimulated glucose uptake and signalling (protein kinase B/Akt and IRS1) in L6 muscle cells. Insulin-induced glucose uptake was reduced from 186 to 141.9 pmol mg−1 min−1 (p < 0.05). 4-HHE induced carbonylation of cell proteins and reduced glutathione concentration from 6.3 to 4.5 nmol/mg protein. Increasing intracellular glutathione pools using D3T prevented 4-HHE-induced carbonyl stress and insulin resistance.Conclusions/interpretation: 4-HHE is produced in type 2 diabetic humans and Zucker diabetic fatty rats and blunts insulin action in skeletal muscle. 4-HHE therefore plays a causal role in the pathophysiology of type 2 diabetes and might constitute a potential therapeutic target to taper oxidative stress-induced insulin resistance. [ABSTRACT FROM AUTHOR]

Published
2018
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53. LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets

Author

Colas, Romain, Sassolas, Agnès, Guichardant, Michel, Cugnet-Anceau, Christine, Moret, Myriam, Moulin, Philippe, Lagarde, Michel, Calzada, Catherine, 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), 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), Fédération d'endocrinologie, Hospices Civils de Lyon (HCL), This study was supported by INSERM and ANR grant (ANR-05-COD-D019-01). RC was funded by the French Ministry of Education and Research. CC is supported by the CNRS., 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), and 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)

Subjects
Oxidized LDL, Platelets, MESH: Signal Transduction, MESH: Lipoproteins, LDL, Lipid peroxidation, MESH: Lipid Peroxidation, LDL, MESH: Metabolic Syndrome X, MESH: Obesity, MESH: Platelet Activation, Obesity, Fatty acids, MESH: Blood Platelets, MESH: Aged, MESH: Middle Aged, MESH: Oxidative Stress, MESH: Humans, MESH: Phospholipases A2, Secretory, MESH: Biological Markers, Type 2 diabetes, MESH: Adult, Metabolic syndrome, MESH: Lipids, MESH: Male, MESH: Arachidonic Acid, lipids (amino acids, peptides, and proteins), [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Diabetes Mellitus, Type 2
Abstract

International audience; AIMS/HYPOTHESIS: This study assessed oxidative stress in LDL from obese patients with the metabolic syndrome and compared it with that in LDL from type 2 diabetic patients or control volunteers. It also determined the effect on platelets of LDL from the three groups. METHODS: The profiles of lipids, fatty acids and fatty acid oxidation products were determined in LDL isolated from plasma of patients with the metabolic syndrome, patients with type 2 diabetes and volunteers (n = 10 per group). The effects of LDL from the participant groups on the platelet arachidonic acid signalling cascade and aggregation were investigated. RESULTS: Compared with LDL from control volunteers, LDL from obese metabolic syndrome and type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and lower ethanolamine plasmalogen levels. Proportions of linoleic acid were decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient groups. Among the markers of lipid peroxidation, oxidation products of linoleic acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59% and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic patients. LDL from metabolic syndrome and type 2 diabetic patients were equally potent in activating the platelet arachidonic acid signalling cascade through increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic phospholipase A(2), and through increased thromboxane B(2) formation. LDL from patients with the metabolic syndrome and type 2 diabetes potentiated platelet aggregation by threefold and 3.5-fold respectively, whereas control LDL had no activating effects on platelets. CONCLUSIONS/INTERPRETATION: The metabolic syndrome in obese patients, without or with diabetes, is associated with increased oxidative stress in LDL, which triggers platelet activation.

Published
2011
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54. Quantification of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal in vegetable and marine lipids

Author

Viau, Michelle, Jouanin, Isabelle, Meynier, Anne, Guichardant, Michel, Genot, Claude, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mécanisme Moléculaire du Diabète (MMD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Saisissez le nom du laboratoire, du service ou du département., Ville service., ProdInra, Migration, Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
[SPI.GPROC] Engineering Sciences [physics]/Chemical and Process Engineering, [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [SDV.IDA] Life Sciences [q-bio]/Food engineering, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2011

55. Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation

Author

Chen, Ping, Véricel, Evelyne, Lagarde, Michel, Guichardant, Michel, 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), INSERM, Ministry of Education and Research, Lipides pour l'Industrie et la Sante (LISA) Carnot Institute, Chinese Educational Council, and Vericel, Evelyne

Subjects
MESH: Humans, MESH: Prostaglandin-Endoperoxide Synthases, MESH: Thromboxanes, MESH: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, MESH: Fatty Acids, Unsaturated, docosahexaenoic acid, docosatrienes, MESH: Arachidonic Acid, MESH: Receptors, Thromboxane, MESH: Cyclooxygenase Inhibitors, MESH: Docosahexaenoic Acids, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Dicarboxylic Acids, 15-lipoxygenase, platelet aggregation, MESH: Platelet Aggregation Inhibitors, MESH: Collagen, MESH: Isomerism, thromboxane receptor, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Oxygen, MESH: Blood Platelets, MESH: Cyclic AMP, MESH: Platelet Aggregation
Abstract

International audience; Docosahexaenoic acid (DHA), an important component of marine lipids, exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as neuroprotectin/protectin D1 [NPD1/PD1; 10(R),17(S)-dihydroxy-docosa-4Z,7Z, 11E,13E,15Z,19Z-hexaenoic acid] produced through the 15-lipoxygenase pathway. However, other metabolites from DHA can be produced through this pathway, and other polyunsaturated fatty acids (PUFAs) of nutritional value may be oxygenated as well. Their biological activities remain unknown. Isomers of protectin D1 were synthesized using soybean lipoxygenase and tested for their ability to inhibit human blood platelet aggregation. A geometric isomer called PDX, previously described with the 11E,13Z,15E geometry, instead of 11E,13E,15Z in PD1, inhibited platelet aggregation at submicromolar concentrations when induced by either collagen, arachidonic acid, or thromboxane. The inhibition occurred at the level of both the cyclooxygenase activity and thromboxane receptor site. Interestingly, all the metabolites tested exhibiting the E,Z,E-conjugated triene were active, whereas E,E,Z trienes (as in PD1) or all-trans (E,E,E) trienes were inactive. We conclude that PDX and other oxygenated products from PUFAs of nutritional interest, having the E,Z,E-conjugated triene motif and collectively named poxytrins (PUFA oxygenated trienes), might have antithrombotic potential.

Published
2011
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57. Phospholipides dans le fluide synovial - influence sur le fonctionnement tribologique des articulations synoviales pathologiques

Author

Corneci, Magdalena, Trunfio-Sfarghiu, Ana-Maria, Dekkiche, Fairouz, Berthier, Yves, Meurisse, Marie-Hélène, Rieu, Jean-Paul, Lagarde, Michel, Guichardant, Michel, Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Faculté de Mécanique, 'Gheorghe Asachi' Technical University of Iasi (TUIASI), Tribologie et Mécanique des Interfaces (TMI), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Laboratoire de Physique de la Matière Condensée et Nanostructures (LPMCN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Département de Chimie, Université Mentouri Constantine [Algérie] (UMC), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), 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)-Centre National de la Recherche Scientifique (CNRS), 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 National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and 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)

Subjects
lipidomic analysis, biotribology, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], synovial joints, phospholipids, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

International audience; Des études récentes ont montré le rôle des assemblages lipidiques associées à la structure discontinue du fluide synovial dans les performances du fonctionnement tribologique d'une articulation saine. Dans le cas des pathologies articulaire, ce fonctionnement est modifié. Ce travail cherche ainsi à identifier l'influence de la variation en composition lipidique des fluides synoviaux pathologiques sur le fonctionnement tribologique des articulations synoviales atteintes de différentes pathologies (arthrite, arthrose)

Published
2010

58. Lipodomic analysis of synovial fluid lubricant in pathlogical articular joints

Author

Corneci, Magdalena, Trunfio-Sfarghiu, Ana-Maria, Berthier, Yves, Meurisse, Marie-Hélène, Rieu, Jean-Paul, Guichardant, Michel, Lagarde, Michel, Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Faculté de Mécanique, 'Gheorghe Asachi' Technical University of Iasi (TUIASI), Tribologie et Mécanique des Interfaces (TMI), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Laboratoire de Physique de la Matière Condensée et Nanostructures (LPMCN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), 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)-Centre National de la Recherche Scientifique (CNRS), Corneci, Magdalena, Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and 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)

Subjects
[SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [PHYS.MECA.BIOM] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

International audience

Published
2008

59. Analyse lipidomique des fluides synoviaux pathologiques pour améliorer le comportement tribologique des articulations pathologiques ou prothésées

Author

Corneci, Magdalena, Trunfio-Sfarghiu, Ana-Maria, Berthier, Yves, Meurisse, Marie-Hélène, Rieu, Jean-Paul, Guichardant, Michel, Lagarde, Michel, Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Faculté de Mécanique, 'Gheorghe Asachi' Technical University of Iasi (TUIASI), Tribologie et Mécanique des Interfaces (TMI), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Laboratoire de Physique de la Matière Condensée et Nanostructures (LPMCN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), 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)-Centre National de la Recherche Scientifique (CNRS), Corneci, Magdalena, Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and 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)

Subjects
[SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [PHYS.MECA.BIOM] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

International audience

Published
2008

60. Nano-Bio-Tribologie: Composition Lipidiques - Influence Sur Le Comportement Tribologique Des Articulations Synoviales Pathologiques

Author

Corneci, Magdalena, Trunfio-Sfarghiu, Ana-Maria, Berthier, Yves, Meurisse, Marie-Hélène, Rieu, Jean-Paul, Guichardant, Michel, Lagarde, Michel, Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Faculté de Mécanique, 'Gheorghe Asachi' Technical University of Iasi (TUIASI), Tribologie et Mécanique des Interfaces (TMI), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Laboratoire de Physique de la Matière Condensée et Nanostructures (LPMCN), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, 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), 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), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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 National de la Recherche Scientifique (CNRS), and Corneci, Magdalena

Subjects
[SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [PHYS.MECA.BIOM] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Published
2008

65. Plasma membrane microdomains from hybrid aspen cells are involved in cell wall polysaccharide biosynthesis

Author

Bessueille, Laurence, Sindt, Nicolas, Guichardant, Michel, Djerbi, Soraya, Teeri, Tuula T., Bulone, Vincent, Bessueille, Laurence, Sindt, Nicolas, Guichardant, Michel, Djerbi, Soraya, Teeri, Tuula T., and Bulone, Vincent

Abstract

Detergent-resistant plasma membrane microdomains [DRMs (detergent-resistant membranes)] were isolated recently from several plant species. As for animal cells, a large range of cellular functions, such as signal transduction, endocytosis and protein trafficking, have been attributed to plant lipid rafts and DRMs. The data available are essentially based on protcomics and more approaches need to be undertaken to elucidate the precise function of individual populations of DRMs in plants. We report here the first isolation of DRMs from purified plasma membranes of a tree species, the hybrid aspen Populus tremula x tremuloides, and their biochemical characterization. Plasma membranes were solubilized with Triton X-100 and the resulting DRMs were isolated by flotation in sucrose density gradients. The DRMs were enriched in sterols, sphingolipids and glycosylphosphatidylinositol-anchored proteins and thus exhibited similar properties to DRMs from other species. However, they contained key carbohydrate synthases involved in cell wall polysaccharide biosynthesis, namely callose [(1 -> 3)-beta-D-glucan] and cellulose synthases. The association of these enzymes with DRMs was demonstrated using specific glucan synthase assays and antibodies, as well as biochemical and chemical approaches for the characterization of the polysaccharides synthesized in vitro by the isolated DRMs. More than 70% of the total glucan synthase activities present in the original plasma membranes was associated with the DRM fraction. In addition to shedding light on the lipid environment of callose and cellulose synthases, our results demonstrate the involvement of DRMs in the biosynthesis of important cell wall polysaccharides. This novel concept suggests a function of plant membrane microdomains in cell growth and morphogenesis., QC 20100525

Published
2009
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67. Bis(Monoacylglycero)Phosphate Accumulation in Macrophages Induces Intracellular Cholesterol Redistribution, Attenuates Liver-X Receptor/ATP-Binding Cassette Transporter A1/ATP-Binding Cassette Transporter G1 Pathway, and Impairs Cholesterol Efflux

Author

Luquain-Costaz, Céline, primary, Lefai, Etienne, additional, Arnal-Levron, Maud, additional, Markina, Daria, additional, Sakaï, Shota, additional, Euthine, Vanessa, additional, Makino, Asami, additional, Guichardant, Michel, additional, Yamashita, Shizuya, additional, Kobayashi, Toshihide, additional, Lagarde, Michel, additional, Moulin, Philippe, additional, and Delton-Vandenbroucke, Isabelle, additional

Published
2013
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68. The Eicosapentaenoic Acid Metabolite 15-Deoxy-δ12,14-Prostaglandin J3 Increases Adiponectin Secretion by Adipocytes Partly via a PPARγ-Dependent Mechanism

Author

Lefils-Lacourtablaise, Jennifer, primary, Socorro, Mairobys, additional, Géloën, Alain, additional, Daira, Patricia, additional, Debard, Cyrille, additional, Loizon, Emmanuelle, additional, Guichardant, Michel, additional, Dominguez, Zury, additional, Vidal, Hubert, additional, Lagarde, Michel, additional, and Bernoud-Hubac, Nathalie, additional

Published
2013
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82. Docosahexaenoic acid, protectin synthesis: relevance against atherothrombogenesis.

Author

Lagarde, Michel, Liu, Miao, Véricel, Evelyne, Calzada, Catherine, Chen, Ping, Driss, Fathi, and Guichardant, Michel

Abstract

DHA is an abundant nutrient from marine lipids: its specific biological effects have been investigated in human volunteers, taking into consideration the dose effects. We report herein that, at dosages below 1 g/d, DHA proved to be effective in lowering blood platelet function and exhibited an ‘antioxidant’ effect. However, this was no longer the case following 1·6 g/d, showing then a U-shape response. The antioxidant effect has been observed in platelets as well as LDL, of which the redox status is assumed to be crucial in their relationship with atherosclerosis. Second, the oxygenated products of DHA, especially protectins produced by lipoxygenases, have been considered for their potential to affect blood platelets and leucocytes. It is concluded that DHA is an interesting nutrient to reduce atherothrombogenesis, possibly through complementary mechanisms involving lipoxygenase products of DHA. [ABSTRACT FROM PUBLISHER]

Published
2014
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88. The Eicosapentaenoic Acid Metabolite 15-Deoxy-δ12,14-Prostaglandin J3 Increases Adiponectin Secretion by Adipocytes Partly via a PPARγ-Dependent Mechanism

Author

Lefils-Lacourtablaise, Jennifer, Socorro, Mairobys, Géloën, Alain, Daira, Patricia, Debard, Cyrille, Loizon, Emmanuelle, Guichardant, Michel, Dominguez, Zury, Vidal, Hubert, Lagarde, Michel, and Bernoud-Hubac, Nathalie

Subjects
EICOSAPENTAENOIC acid, PROSTAGLANDINS, FAT cells, FOOD consumption, LIPID metabolism, MOLECULAR structure, LABORATORY mice, EICOSANOIDS
Abstract

The intake of ω-3 polyunsaturated fatty acids (PUFAs), which are abundant in marine fish meat and oil, has been shown to exert many beneficial effects. The mechanisms behind those effects are numerous, including interference with the arachidonic acid cascade that produces pro-inflammatory eicosanoids, formation of novel bioactive lipid mediators, and change in the pattern of secreted adipocytokines. In our study, we show that eicosapentaenoic acid (EPA) increases secreted adiponectin from 3T3-L1 adipocytes and in plasma of mice as early as 4 days after initiation of an EPA-rich diet. Using 3T3-L1 adipocytes, we report for the first time that 15-deoxy-δ12,14-PGJ3 (15d-PGJ3), a product of EPA, also increases the secretion of adiponectin. We demonstrate that the increased adiponectin secretion induced by 15d-PGJ3 is partially peroxisome proliferator-activated receptor-gamma (PPAR-γ)-mediated. Finally, we show that 3T3-L1 adipocytes can synthesize 15d-PGJ3 from EPA. 15d-PGJ3 was also detected in adipose tissue from EPA-fed mice. Thus, these studies provide a novel mechanism(s) for the therapeutic benefits of ω-3 polyunsaturated fatty acids dietary supplementation. [ABSTRACT FROM AUTHOR]

Published
2013
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89. Depressed Levels of Prostaglandin F2α in Mice Lacking Akr1b7 Increase Basal Adiposity and Predispose to Diet-Induced Obesity.

Author

Volat, Fanny E., Pointud, Jean-Christophe, Pastel, Emilie, Morio, Béatrice, Sion, Benoit, Hamard, Ghislaine, Guichardant, Michel, Colas, Romain, Lefrançois-Martinez, Anne-Marie, and Martinez, Antoine

Subjects
ADIPOSE tissues, PROSTAGLANDINS, OBESITY risk factors, HYPOGLYCEMIC agents, INSULIN resistance, CELL lines, CLOPROSTENOL
Abstract

Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F2α (PGF2α) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF2α synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7-/- mice in 129/Sv background. Akr1b7-/- mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF2α WAT contents. Cloprostenol (PGF2α agonist) administration to Akr1b7-/- mice normalized WAT expansion by affecting both de novo adipocyte differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7-/- mice with cloprostenol suggested that decreased adipocyte size resulted from inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of WAT development through at least two PGF2α-dependent mechanisms: inhibition of adipogenesis and lipogenesis. These findings provide molecular rationale to explore the status of aldo-keto reductases in dysregulations of adipose tissue homeostasis. [ABSTRACT FROM AUTHOR]

Published
2012
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90. The natural protective mechanism against hyperglycemia in vascular endothelial cells: roles of the lipid peroxidation product 4-hydroxydodecadienal and peroxisome proliferator-activated receptor delta.

Author

Riahi Y, Sin-Malia Y, Cohen G, Alpert E, Gruzman A, Eckel J, Staels B, Guichardant M, Sasson S, Riahi, Yael, Sin-Malia, Yoav, Cohen, Guy, Alpert, Evgenia, Gruzman, Arie, Eckel, Juergen, Staels, Bart, Guichardant, Michel, and Sasson, Shlomo

Abstract

Objective: Vascular endothelial cells (VECs) downregulate their rate of glucose uptake in response to hyperglycemia by decreasing the expression of their typical glucose transporter GLUT-1. Hitherto, we discovered critical roles for the protein calreticulin and the arachidonic acid-metabolizing enzyme 12-lipoxygenase in this autoregulatory process. The hypothesis that 4-hydroxydodeca-(2E,6Z)-dienal (4-HDDE), the peroxidation product of 12-lipoxygenase, mediates this downregulatory mechanism by activating peroxisome proliferator-activated receptor (PPAR) delta was investigated.Research Design and Methods: Effects of 4-HDDE and PPARdelta on the glucose transport system and calreticulin expression in primary bovine aortic endothelial cells were evaluated by pharmacological and molecular interventions.Results: Using GW501516 (PPARdelta agonist) and GSK0660 (PPARdelta antagonist), we discovered that high-glucose-induced downregulation of the glucose transport system in VECs is mediated by PPARdelta. A PPAR-sensitive luciferase reporter assay in VECs revealed that high glucose markedly increased luciferase activity, while GSK0660 abolished it. High-performance liquid chromatography analysis showed that high-glucose incubation substantially elevated the generation of 4-HDDE in VECs. Treatment of VECs, exposed to normal glucose, with 4-HDDE mimicked high glucose and downregulated the glucose transport system and increased calreticulin expression. Like high glucose, 4-HDDE significantly activated PPARdelta in cells overexpressing human PPAR (hPPAR)delta but not hPPARalpha, -gamma1, or -gamma2. Moreover, silencing of PPARdelta prevented high-glucose-dependent alterations in GLUT-1 and calreticulin expression. Finally, specific binding of PPARdelta to a PPAR response element in the promoter region of the calreticulin gene was identified by utilizing a specific chromatin immunoprecipitation assay.Conclusions: Collectively, our data show that 4-HDDE plays a central role in the downregulation of glucose uptake in VECs by activating PPARdelta. [ABSTRACT FROM AUTHOR]

Published
2010
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91. Bis-allylic Deuterated DHA Alleviates Oxidative Stress in Retinal Epithelial Cells.

Author

Rosell, Mélissa, Giera, Martin, Brabet, Philippe, Shchepinov, Mikhail S., Guichardant, Michel, Durand, Thierry, Vercauteren, Joseph, Galano, Jean-Marie, and Crauste, Céline

Subjects
EPITHELIAL cells, DEUTERATION, OXIDATIVE stress, RHODOPSIN, DOCOSAHEXAENOIC acid, RETINAL diseases, BIOLOGICAL pigments
Abstract

Oxidative stress plays a crucial role in developing and accelerating retinal diseases including age-related macular degeneration (AMD). Docosahexaenoic acid (DHA, C22:6, n-3), the main lipid constituent of retinal epithelial cell membranes, is highly prone to radical and enzymatic oxidation leading to deleterious or beneficial metabolites for retinal tissue. To inhibit radical oxidation while preserving enzymatic metabolism, deuterium was incorporated at specific positions of DHA, resulting in D2-DHA when incorporated at position 6 and D4-DHA when incorporated at the 6,9 bis-allylic positions. Both derivatives were able to decrease DHAs' toxicity and free radical processes involved in lipid peroxidation, in ARPE-19 cells (Adult Retinal Pigment Epithelial cell line), under pro-oxidant conditions. Our positive results encouraged us to prepare lipophenolic-deuterated-DHA conjugates as possible drug candidates for AMD treatment. These novel derivatives proved efficient in limiting lipid peroxidation in ARPE-19 cells. Finally, we evaluated the underlying mechanisms and the enzymatic conversion of both deuterated DHA. While radical abstraction was affected at the deuterium incorporation sites, enzymatic conversion by the lipoxygenase 15s-LOX was not impacted. Our results suggest that site-specifically deuterated DHA could be used in the development of DHA conjugates for treatment of oxidative stress driven diseases, or as biological tools to study the roles, activities and mechanisms of DHA metabolites. [ABSTRACT FROM AUTHOR]

Published
2019
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99. Physiological and pathological roles of FATP-mediated lipid droplets in Drosophila and mice retina

Author

Michel Guichardant, Laurent Guillou, Victor Girard, Bertrand Mollereau, Nathalie Bernoud-Hubac, Aurélie Cubizolle, Daan M. Van Den Brink, Claire Angebault-Prouteau, Pierre Dourlen, Gilles Chatelain, Philippe Brabet, Francesco Napoletano, Simone Johansen, Nathalie Davoust, Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS 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), BioSciences Lyon-Gerland (BLG), 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-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Life Sciences, Trieste, University of Trieste, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), 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), French National Research Agency ANR-12-BSV1-0019-02, Association Francaise contre les Myopathies, a European Union's Seventh Framework Programme/AIRC (Associazione Italiana per la Ricerca sul cancro) Reintegration Grant, Bloomington Drosophila Stock Center NIH P40OD018537, CarMeN, laboratoire, Institut des Neurosciences de Montpellier (INM), Università degli studi di Trieste = University of Trieste, 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), Van Den Brink, Daan M., Cubizolle, Aurélie, Chatelain, Gille, Davoust, Nathalie, Girard, Victor, Johansen, Simone, Napoletano, Francesco, Dourlen, Pierre, Guillou, Laurent, Angebault-Prouteau, Claire, Bernoud-Hubac, Nathalie, Guichardant, Michel, Brabet, Philippe, Mollereau, Bertrand, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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)

Subjects
Pigments, Aging, Sensory Receptors, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Genetics, Genetics (clinical), Cancer Research, Social Sciences, Biochemistry, Mice, 0302 clinical medicine, Animal Cells, acyltransferase, Psychology, Energy-Producing Organelles, Neurons, Genetics & Heredity, Drosophila Melanogaster, Neurodegeneration, Eukaryota, Fatty Acid Transport Proteins, Lipids, Cell biology, drosophile, [SDV] Life Sciences [q-bio], Physical Sciences, gouttelette lipidique, Cellular Types, Cellular Structures and Organelles, photoreceptor differentiation, Visual phototransduction, Evolution, Ocular Anatomy, Materials Science, Retina, 03 medical and health sciences, Genetic, Vesicles, Materials by Attribute, Organisms, Biology and Life Sciences, Lipid Droplets, Lipid Metabolism, medicine.disease, Invertebrates, Ecology, Evolution, Behavior and Systematic, Mice, Inbred C57BL, 030104 developmental biology, age, Eyes, Reactive Oxygen Species, 030217 neurology & neurosurgery, Neuroscience, Photoreceptors, 0301 basic medicine, [SDV]Life Sciences [q-bio], Mitochondrion, souris, medicine.disease_cause, retine, Animals, Genetically Modified, Lipid droplet, Medicine and Health Sciences, Drosophila Proteins, Ecology, neurodegeneration, Animal Models, Mitochondria, Insects, medicine.anatomical_structure, Experimental Organism Systems, Drosophila, Sensory Perception, Anatomy, Research Article, Signal Transduction, Programmed cell death, Arthropoda, lcsh:QH426-470, Bioenergetics, Biology, Research and Analysis Methods, visual cycle, storage, Model Organisms, Behavior and Systematics, Ocular System, Coenzyme A Ligases, medicine, Animals, programmed cell-death, disease, acid transport proteins, Afferent Neurons, Lipid metabolism, Cell Biology, pigment epithelium, Oxidative Stress, lcsh:Genetics, rôle physiologique, Cellular Neuroscience, sense organs, Energy Metabolism, Head, Oxidative stress
Abstract

Increasing evidence suggests that dysregulation of lipid metabolism is associated with neurodegeneration in retinal diseases such as age-related macular degeneration and in brain disorders such as Alzheimer’s and Parkinson’s diseases. Lipid storage organelles (lipid droplets, LDs), accumulate in many cell types in response to stress, and it is now clear that LDs function not only as lipid stores but also as dynamic regulators of the stress response. However, whether these LDs are always protective or can also be deleterious to the cell is unknown. Here, we investigated the consequences of LD accumulation on retinal cell homeostasis under physiological and stress conditions in Drosophila and in mice. In wild-type Drosophila, we show that dFatp is required and sufficient for expansion of LD size in retinal pigment cells (RPCs) and that LDs in RPCs are required for photoreceptor survival during aging. Similarly, in mice, LD accumulation induced by RPC-specific expression of human FATP1 was non-toxic and promoted mitochondrial energy metabolism in RPCs and non-autonomously in photoreceptor cells. In contrast, the inhibition of LD accumulation by dFatp knockdown suppressed neurodegeneration in Aats-metFB Drosophila mutants, which carry elevated levels of reactive oxygen species (ROS). This suggests that abnormal turnover of LD may be toxic for photoreceptors cells of the retina under oxidative stress. Collectively, these findings indicate that FATP-mediated LD formation in RPCs promotes RPC and neuronal homeostasis under physiological conditions but could be deleterious for the photoreceptors under pathological conditions., Author summary Lipids are major cell constituents and are present in the membranes, as free lipids in the cytoplasm, or stored in vesicles called lipid droplets (LDs). Under conditions of stress, lipids stored in LDs can be released to serve as substrates for energy metabolism by mitochondria. However, lipid storage is dysregulated in many degenerative disorders such as age-related macular degeneration, Parkinson’s and Alzheimer’s diseases. Thus, it is unclear whether accumulation of LDs is protective or toxic for neuronal cells. To address this question, we examined the consequences of removal or enforced LD accumulation on the health of retinal cells in flies and mice. Like humans, fly and mouse retinas contain retinal pigment cells (RPC) that support the functions of neighboring photoreceptor cells. We found that overexpression of the fatty acid transport protein (FATP) in RPCs induced accumulation of LDs in both transgenic flies and mice. Moreover, LD accumulation in RPCs was not harmful for juxtaposed photoreceptors during aging, but was toxic under stress conditions. We propose that lipid storage promotes cellular communication that affects photoreceptor health.

Published
2018
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100. The Modification and Performance of a Large Animal Anesthesia Machine (Tafonius ® ) in Order to Deliver Xenon to a Horse.

Author

Santangelo B, Robin A, Simpson K, Potier J, Guichardant M, and Portier K

Abstract

Introduction: Xenon, due to its interesting anesthetic properties, could improve the quality of anesthesia protocols in horses despite its high price. This study aimed to modify and test an anesthesia machine capable of delivering xenon to a horse., Materials and Methods: An equine anesthesia machine (Tafonius, Vetronic Services Ltd., UK) was modified by including a T-connector in the valve block to introduce xenon, so that the xenon was pushed into the machine cylinder by the expired gases. A xenon analyzer was connected to the expiratory limb of the patient circuit. The operation of the machine was modeled and experimentally tested for denitrogenation, wash-in, and maintenance phases. The system was considered to consist of two compartments, one being the horse's lungs, the other being the machine cylinder and circuit. A 15-year-old, 514-kg, healthy gelding horse was anesthetized for 70 min using acepromazine, romifidine, morphine, diazepam, and ketamine. Anesthesia was maintained with xenon and oxygen, co-administered with lidocaine. Ventilation was controlled. Cardiorespiratory variables, expired fraction of xenon (FeXe), blood gases were measured and xenon was detected in plasma. Recovery was unassisted and recorded., Results: FeXe remained around 65%, using a xenon total volume of 250 L. Five additional boli of ketamine were required to maintain anesthesia. PaO 2 was 45 ± 1 mmHg. The recovery was calm. Xenon was detected in blood during the entire administration time., Conclusion: This pilot study describes how to deliver xenon to a horse. Although many technical problems were encountered, their correction could guide future endeavors to study the use of xenon in horses.

Published
2017
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