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1. Bioavailability and spatial distribution of fatty acids in the rat retina after dietary omega-3 supplementation

Author

William C. Gordon, Spiro Khoury, Lionel Bretillon, Marie-Annick Maire, Niyazi Acar, Stéphane Grégoire, Bokkyoo Jun, Elisa Vidal, Lucy Martine, Stéphanie Cabaret, Nicolas G. Bazan, Olivier Berdeaux, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), LSU Health Sciences Center, and The American Society for Biochemistry and Molecular Biology, Inc.

Subjects
Male, 0301 basic medicine, eicosapentaenoic acid, genetic structures, [SDV]Life Sciences [q-bio], lipid spatial organization, Biological Availability, QD415-436, 030204 cardiovascular system & hematology, fatty acids, Biochemistry, Retina, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, lipid, Phosphatidylcholine, Fatty Acids, Omega-3, medicine, Animals, very long chain polyunsaturated, Food science, phosphatidylcholine, triglycerides, phospholipids, Research Articles, spatial organization, chemistry.chemical_classification, omega-3 fatty acids, Chemistry, lipid biochemistry, food and beverages, Cell Biology, docosahexaenoic acid, Eicosapentaenoic acid, eye diseases, Rats, Bioavailability, 030104 developmental biology, medicine.anatomical_structure, Human nutrition, Docosahexaenoic acid, lipids (amino acids, peptides, and proteins), Composition (visual arts), diet and dietary lipids, sense organs, Polyunsaturated fatty acid
Abstract

International audience; Spatial changes of fatty acids in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids, EPA-containing triglycerides, DHA-containing phospholipids, or DHA-containing triglycerides. Qualitative changes in fatty acid composition of plasma, erythrocytes and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species in retina were determined by liquid chromatography coupled to tandem mass spectrometry and MALDI (Matrix Assisted Laser Desorption Ionization) coupled to mass spectrometry imaging. The omega-3 content in the lipids of plasma and erythrocytes suggests that phospholipids as well as triglycerides are good omega-3 carriers for retina. However, a significant increase in DHA content in retina was observed, especially molecular species as di-DHA-containing PC and PE, as well as an increase in very long chain polyunsaturated fatty acids (VLC-PUFAs, more than 28 carbons) following phospholipid-EPA and triglyceride-DHA diets only. All supplemented diets triggered spatial organization changes of DHA in the photoreceptor layer around the optic nerve. Taken together, these findings suggest that dietary omega-3 supplementation can modify the content of fatty acids in the rat retina.

Published
2020

2. Profile of Fatty Acids, Tocopherols, Phytosterols and Polyphenols in Mediterranean Oils (Argan Oils, Olive Oils, Milk Thistle Seed Oils and Nigella Seed Oil) and Evaluation of their Antioxidant and Cytoprotective Activities

Author

John J. Mackrill, Stéphane Grégoire, Amira Zarrouk, Gérard Lizard, Mohamed Hammami, Lucy Martine, Mondher Mejri, Asmaa Badreddine, Aline Yammine, Boubker Nasser, Thomas Nury, Emmanuelle Camus, Wiem Meddeb, Mustapha Cherkaoui-Malki, Philippe Durand, Amira Namsi, Lionel Bretillon, Université de Monastir (Université de Monastir), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique (Bio-PeroxIL), Université de Bourgogne (UB), Institut Supérieur de Biotechnologie, Laboratoire de Recherche Appliquée Spiral [Bourgogne] (LARA SPIRAL), Université Hassan 1er [Settat], University College Cork (UCC), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), BASIM (Association Bourguignonne pour les Applications des Sciences de l'Information en Medecine), and COST (European Cooperation in Science and Technology) CA16112

Subjects
0301 basic medicine, Antioxidant, medicine.medical_treatment, Linoleic acid, mediterranean oils, Tocopherols, Antioxidants, Cell Line, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Drug Discovery, medicine, Animals, Humans, Milk Thistle, Plant Oils, Food science, cytoprotective activities, Olive Oil, Nigella, 2. Zero hunger, Pharmacology, biology, Phytosterol, Fatty Acids, Phytosterols, Polyphenols, food and beverages, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, biology.organism_classification, antioxidant properties, Oleic acid, 030104 developmental biology, Spinasterol, chemistry, Polyphenol, 030220 oncology & carcinogenesis, Seeds, Hydroxytyrosol, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Background: The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined. Objective: To establish and compare the fatty acid, tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO). Methods: The biochemical profiles were determined by gas chromatography-flame ionization, high performance liquid chromatography and gas chromatography, coupled with mass spectrometry as required. The antioxidant and cytoprotective activities were evaluated with the KRL (Kit Radicaux Libres) and the fluorescein diacetate tests on nerve cells treated with 7-ketocholesterol (7KC). Results: The fatty acid profile revealed high linoleic acid (C18:2 n-6) content in AO, OO, MTSO and NSO. The highest levels of oleic acid (C18:1 n-9) were found in AO and OO. The tocopherol profile showed that Agadir AO contained the highest amount of α-tocopherol, also present at high level in MTSO and Tunisian OO; Berkane AO was rich in γ-tocopherol. The phytosterol profile indicated that β-sitosterol was predominant in the oils, except AO; spinasterol was only present in AO. Polyphenol profiles underlined that OO was the richest in polyphenols; hydroxytyrosol was only found in OO; few polyphenols were detected in AO. The oils studied have antioxidant activities, and all of them, except NSO, prevented 7KC-induced cell death. The antioxidant characteristics of AO were positively correlated with procatechic acid and compestanol levels. Conclusion: Based on their biochemical profiles, antioxidant and cytoprotective characteristics, AO, OO, and MTSO are potentially beneficial to human health.

Published
2019

3. Soluble fiber inulin consumption limits alterations of the gut microbiota and hepatic fatty acid metabolism caused by high-fat diet

Author

Mayssa Albouery, Benoit Chassaing, Marie-Agnès Bringer, Alexis Bretin, Stéphane Grégoire, Niyazi Acar, Ségolène Gambert, Alain M. Bron, Lucy Martine, Bénédicte Buteau, Julien, Sabine, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Georgia State University, University System of Georgia (USG), Laboratoire de biochimie médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Laboratoire de biochimie médicale (CHU Dijon)

Subjects
Blood Glucose, Dietary Fiber, Male, 0301 basic medicine, Gut flora, Mice, chemistry.chemical_compound, RNA, Ribosomal, 16S, Food science, Diet, Fat-Restricted, 2. Zero hunger, chemistry.chemical_classification, Nutrition and Dietetics, biology, inulin, food and beverages, 3. Good health, high-fat diet, Fatty Acids, Unsaturated, Soluble fiber, Composition (visual arts), lipids (amino acids, peptides, and proteins), lcsh:Nutrition. Foods and food supply, Polyunsaturated fatty acid, fiber, Inulin, lcsh:TX341-641, Diet, High-Fat, liver, fatty acids, Article, metabolic syndrome, 03 medical and health sciences, lipid, medicine, microbiota, Animals, Triglycerides, 030109 nutrition & dietetics, Fatty acid metabolism, Cholesterol, HDL, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cholesterol, LDL, Metabolism, Lipid Metabolism, biology.organism_classification, medicine.disease, Dietary Fats, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Gastrointestinal Microbiome, Mice, Inbred C57BL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, chemistry, Metabolic syndrome, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract

International audience; Diet shapes the gut microbiota which impacts hepatic lipid metabolism. Modifications in liver fat content are associated with metabolic disorders. We investigated the extent of dietary fat and fiber-induced alterations in the composition of gut microbiota and hepatic fatty acids (FAs). Mice were fed a purified low-fat diet (LFD) or high-fat diet (HFD) containing non-soluble fiber cellulose or soluble fiber inulin. HFD induced hepatic decreases in the amounts of C14:0, C16:1n-7, C18:1n-7 and increases in the amounts of C17:0, C20:0, C16:1n-9, C22:5n-3, C20:2n-6, C20:3n-6, and C22:4n-6. When incorporated in a LFD, inulin poorly affected the profile of FAs. However, when incorporated in a HFD, it (i) specifically led to an increase in the amounts of hepatic C18:0, C22:0, total polyunsaturated FAs (PUFAs), total n-6 PUFAs, C18:3n-3, and C18:2n-6, (ii) exacerbated the HFD-induced increase in the amount of C17:0, and (iii) prevented the HFD-induced increases in C16:1n-9 and C20:3n-6. Importantly, the expression/activity of some elongases and desaturases, as well as the gut microbiota composition, were impacted by the dietary fat and fiber content. To conclude, inulin modulated gut microbiota and hepatic fatty acid composition, and further investigations will determine whether a causal relationship exists between these two parameters.

Published
2021

4. Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition

Author

Mayssa Albouery, Bénédicte Buteau, Stéphane Grégoire, Claire Cherbuy, Jean-Paul Pais de Barros, Lucy Martine, Florian Chain, Stéphanie Cabaret, Olivier Berdeaux, Alain M. Bron, Niyazi Acar, Philippe Langella, Marie-Agnès Bringer, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AgroParisTech, Equipe LIPNESS (LNC - U1231) (LIPNESS), Lipides - Nutrition - Cancer [Dijon - U1231] (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-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, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Agence Nationale de la Recherche [ANR-11-LABX-0021-01], INRA, Conseil Régional Bourgogne, Franche-Comté [PARI grant], and FEDER (European Funding for Regional Economical Development), Fondation de France/Fondation de l'oeil., ProdInra, Migration, and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Fatty Acid Desaturases, Male, 0301 basic medicine, lcsh:QR1-502, Gene Expression, Gut flora, lcsh:Microbiology, Fatty Acids, Monounsaturated, Mice, Cellular and Infection Microbiology, Aging brain, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Original Research, chemistry.chemical_classification, Fatty Acids, Age Factors, Brain, Lipids, cortex, Infectious Diseases, Fatty Acids, Unsaturated, [SDV.IMM]Life Sciences [q-bio]/Immunology, lipids (amino acids, peptides, and proteins), Sphingomyelin, Stearoyl-CoA Desaturase, Polyunsaturated fatty acid, Microbiology (medical), medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Fatty Acid Elongases, FADS1, FADS2, 030106 microbiology, Immunology, Biology, liver, digestive system, Microbiology, 03 medical and health sciences, lipid, Internal medicine, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, microbiota, Animals, Germ-Free Life, phospholipid, aging, Fatty acid, cholesterol, Lipid Metabolism, biology.organism_classification, Gastrointestinal Microbiome, Transplantation, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, Endocrinology, chemistry, fatty acid, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

PMCID: PMC6970973; International audience; Understanding the molecular mechanisms underlying the changes observed during aging is a prerequisite to design strategies to prevent age-related diseases. Aging is associated with metabolic changes, including alteration in the brain lipid metabolism. These alterations may contribute to the development of pathophysiological conditions. Modifications in the gut microbiota composition are also observed during aging. As communication axes exist between the gut microbiota and the brain and knowing that microbiota influences the host metabolism, we speculated on whether age-associated modifications in the gut microbiota could be involved in the lipid changes observed in aging brain. For that purpose, germ-free mice were colonized by the fecal microbiota of young or old donor mice. Lipid classes and fatty acid profiles were determined in the brain (cortex), plasma and liver by thin-layer chromatography on silica gel-coated quartz rods and gas chromatography. Gut colonization by microbiota of old mice resulted in a significant increase in total monounsaturated fatty acids (MUFA) and a significant decrease in the relative amounts of cholesterol and total polyunsaturated fatty acids (PUFA) in the cortex. Among the eight most represented fatty acids in the cortex, the relative abundances of five (C18:1n-9, C22:6n-3, C20:4n-6, C18:1n-7, and C20:1n-9) were significantly altered in mice inoculated with an aged microbiota. Liquid chromatography analyses revealed that the relative abundance of major species among phosphatidyl and plasmenylcholine (PC 16:0/18:1), phosphatidyl and plasmenylethanolamine (PE 18:0/22:6), lysophosphatidylethanolamine (LPE 22:6) and sphingomyelins (SM d18:1/18:0) were significantly altered in the cortex of mice colonized by the microbiota obtained from aged donors. Transplantation of microbiota from old mice also modified the lipid class and fatty acid content in the liver. Finally, we found that the expression of several genes involved in MUFA and PUFA synthesis (Scd1, Fads1, Fads2, Elovl2, and Elovl5) was dysregulated in mice inoculated with an aged microbiota. In conclusion, our data suggest that changes in gut microbiota that are associated with aging can impact brain and liver lipid metabolisms. Lipid changes induced by an aged microbiota recapitulate some features of aging, thus pointing out the potential role of microbiota alterations in the age-related degradation of the health status.

Published
2020
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5. Impact of a high-fat diet on the fatty acid composition of the retina

Author

Benoit Chassaing, Marie-Agnès Bringer, Mayssa Albouery, Bénédicte Buteau, Niyazi Acar, Lucy Martine, Ségolène Gambert, Stéphane Grégoire, Alain M. Bron, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de biochimie médicale (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Ophtalmologie (CHU de Dijon), Georgia State University, University System of Georgia (USG), Inserm U1016, Paris Descartes University, The Agence Nationale de la Recherche [ANR-11-LABX-0021-01], INRAE, the Conseil Régional de Bourgogne, Franche-Comté [PARI grant], the FEDER (European Funding for Regional Economical Development), and the Fondation de France/Fondation de l'oeil., and Laboratoire de biochimie médicale (CHU de Dijon)

Subjects
Blood Glucose, Male, 0301 basic medicine, retina, Weight Gain, Fatty Acids, Monounsaturated, Mice, chemistry.chemical_compound, 0302 clinical medicine, Adiposity, chemistry.chemical_classification, Fatty Acids, monounsaturated fatty acids, alpha-Linolenic Acid, food and beverages, Sensory Systems, high-fat diet, Linoleic Acids, Liver, Fatty Acids, Unsaturated, lipids (amino acids, peptides, and proteins), medicine.symptom, plasmalogens, Polyunsaturated fatty acid, polyunsaturated fatty acids, medicine.medical_specialty, Chromatography, Gas, Linoleic acid, essential fatty acids, Diet, High-Fat, metabolic syndrome, 03 medical and health sciences, Cellular and Molecular Neuroscience, Diabetes mellitus, Internal medicine, medicine, Animals, saturated fatty acids, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Dyslipidemias, nutritional and metabolic diseases, Fatty acid, Retinal, medicine.disease, Mice, Inbred C57BL, Ophthalmology, 030104 developmental biology, Endocrinology, chemistry, Hyperglycemia, 030221 ophthalmology & optometry, sense organs, Metabolic syndrome, Weight gain, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Dyslipidemia
Abstract

Structure and function of the retina mainly rely on its fatty acid (FA) composition. Evidence from epidemiological studies and from animal experiments indicates that FA composition of the retina is influenced by the diet. Mice under chronic high-fat diet (HFD) develop metabolic syndrome, a risk factor for diabetes that is associated with structural and functional alterations of the retina. Here, we studied the impact of chronic exposure of mice to HFD on retinal FA composition. C57BL/6 J male mice were fed either a chow diet or a HFD for 11 weeks. As expected, HFD induced weight gain, adiposity, hyperglycemia and dyslipidemia. The retinal FA composition was determined by gas chromatography coupled to flame ionization detection. No significant change in the relative abundance of total saturated FAs (SFAs), total monounsaturated FAs (MUFAs) or total polyunsaturated FAs (PUFAs) was observed. However, retinas of HFD-fed mice displayed decreased amounts of C24:0 (p = 0.0231), C16:1n-7 (p < 0.0001), C18:1n-7 (p < 0.0001), C20:3n-9 (p = 0.0425) and C20:3n-6 (p = 0.0008), and an increased amount of C20:2n-6 (p < 0.0001). In addition, the ratio of linoleic acid (C18:2n-6) to alpha-linolenic acid (C18:3n-3) was increased in the retinas of HFD-fed mice (15.0 +/- 0.8 versus 11.8 +/- 0.6 in HFD and CD, respectively, p = 0.0045). No modification in the contents of arachidonic acid (C20:4n-6, AA) and docosahexaenoic acid (C22:6n-3, DHA) were observed. Analysis of dimethylacetals (DMA), which are residues of plasmalogens (Pls), revealed that the amount of Pls containing octadecanal-aldehydes (DMA C18:0) was significantly increased in HFD-fed mice (p = 0.0447). This increase was, at least in part, balanced by a decrease in Pls containing 7-octadecanal-aldehydes (DMA C18:1n-7) (p = 0.0007). In conclusion, HFD had an impact on the relative proportion of essential dietary fatty acids linoleic acid and alpha-linolenic acid that are incorporated in the retina. However, this imbalance in PUFA precursors did not alter the content of the two major retinal long-chain PUFAs, AA and DHA. HFD consumption also led to alterations in the retinal SFAs, MUFAs and Pls profiles.

Published
2020
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6. Is 24(S)-hydroxycholesterol a potent modulator of cholesterol metabolism in Müller cells? An in vitro study about neuron to glia communication in the retina

Author

Elise Léger-Charnay, Ségolène Gambert, Lionel Bretillon, Lucy Martine, Bénédicte Buteau, Elodie Masson, Laurent Leclere, Tristan Morala, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Biochimie médicale A, Université Bordeaux Segalen - Bordeaux 2, The Institut National de la Recherche Agronomique, the Conseil Régional Bourgogne, Franche-Comté (PARI grant), the FEDER (European Funding for Regional Economical Development), the Fondation de France/Fondation de l’œil, the Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation, the Université de Bourgogne Franche-Comté, and and the Nouvelle Société Française d’Athérosclérose.

Subjects
0301 basic medicine, Apolipoprotein E, Oxysterol, Ependymoglial Cells, Retinal ganglion, Retina, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Desmosterol, CYP27A1, medicine, Animals, Rats, Long-Evans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Neurons, biology, Chemistry, Cholesterol, Sensory Systems, Hydroxycholesterols, 3. Good health, Cell biology, Rats, Ophthalmology, 030104 developmental biology, medicine.anatomical_structure, ABCA1, Models, Animal, 030221 ophthalmology & optometry, biology.protein, lipids (amino acids, peptides, and proteins), sense organs, Neuron, Neuroglia, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Communication between neurons and glia plays a major role in nervous tissue homeostasis. It is thought to participate in tuning cholesterol metabolism to cellular demand, which is a critical issue for neuronal health. Cholesterol is a membrane lipid crucial for nervous tissue functioning, and perturbed regulation of its metabolism has been linked to several neurodegenerative disorders. In the brain, 24(S)-hydroxycholesterol (24S-OHC) is an oxysterol synthesized by neurons to eliminate cholesterol, and 24S-OHC has been shown to regulate cholesterol metabolism in astrocytes, glial cells which provide cholesterol to neurons. In the retina, 24S-OHC is also an elimination product of cholesterol produced by neurons, especially the retinal ganglion cells. However, it is not known whether Muller cells, the major macroglial cells of the retina, play the role of cholesterol provider for retinal neurons and whether they respond to 24S-OHC signaling, similarly to brain glial cells. In the present study, primary cultures of rat Muller cells were treated with 0, 0.5 or 1.5 μM 24S-OHC for 48 hours. The levels of cholesterol, precursors and oxysterols were quantified using gas chromatography coupled to flame-ionization detection or mass spectrometry. In addition, the expression of key genes related to cholesterol metabolism was analyzed using RTq-PCR. Muller cells were shown to express many genes linked to cholesterol metabolism, including genes coding for proteins implicated in cholesterol biosynthesis (HMGCR), cholesterol uptake and export via lipoproteins (LDL-R, SR-BI, ApoE and ABACA1) and regulation of cholesterol metabolism (SREBP2 and LXRβ). Cholesterol and several of its precursors and oxidative products were present. CYP27A1, the main retinal enzyme implicated in cholesterol elimination via oxysterol production, was quantified at low transcript levels but neither of its two typical products were detected in Muller cells. Furthermore, our results demonstrate that 24S-OHC has a strong hypocholesterolemic effect in Muller cells, leading to cholesterol depletion (-37 % at 1.5 μM). This was mediated by a decrease in cholesterol synthesis, as illustrated by reduced levels of cholesterol precursors: desmosterol (-38 % at 1.5 μM) and lathosterol (-84 % at 1.5 μM), and strong downregulation of HMGCR gene expression (2.4 fold decrease at 1.5μM). In addition, LDL-R and SR-BI gene expression were reduced in response to 24S-OHC treatment (2 fold and 1.6 fold at 1.5 μM, respectively), suggesting diminished lipoprotein uptake by the cells. On the contrary, there was a dramatic overexpression of ABCA1 transporter (10 fold increase at 1.5 μM), probably mediating an increase in cholesterol efflux. Finally, 24S-OHC induced a small but significant upregulation of the CYP27A1 gene. These data indicate that Muller cells possess the necessary cholesterol metabolism machinery and that they are able to sharply adjust their cholesterol metabolism in response to 24S-OHC, a signal molecule of neuronal cholesterol status. This suggests that Muller cells could be major players of cholesterol homeostasis in the retina via neuron-glia crosstalk.

Published
2019

7. Causal Link between n-3 Polyunsaturated Fatty Acid Deficiency and Motivation Deficits

Author

Olivier Berdeaux, Elodie Masson, Stéphane Grégoire, Roman Walle, Véronique De Smedt-Peyrusse, Lucy Martine, Frank Aby, Clémentine Bosch-Bouju, Baptiste Caraballo, Suzanne van der Veldt, David W.L. Ma, Xavier Fioramonti, Jean-Christophe Helbling, Jing X. Kang, Sophie Layé, Gabriel Barreda-Gómez, Pierre Trifilieff, Sylvie Vancassel, Stéphanie Cabaret, Guillaume Ferreira, Marie-Lou Boyer, Tarson Tolentino-Cortez, Fabien Ducrocq, Asma Oummadi, Andrea Contini, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), IMG Pharma Biotech S.L., Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Massachusetts General Hospital, Harvard Medical School [Boston] (HMS), University of Guelph, Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Partenaires INRAE, Université de Bourgogne (UB), Massachusetts General Hospital [Boston], and Department of Human Health and Nutritional Sciences

Subjects
Male, 0301 basic medicine, N-3 PUFA, Physiology, [SDV]Life Sciences [q-bio], Dopamine, Mice, Transgenic, Nucleus accumbens, Medium spiny neuron, Mice, 03 medical and health sciences, 0302 clinical medicine, Dopamine receptor D2, Fatty Acids, Omega-3, medicine, Animals, Molecular Biology, Pathological, 030304 developmental biology, Neurons, Medium spiny neurons, chemistry.chemical_classification, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Motivation, Receptors, Dopamine D2, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Cell Biology, Mice, Inbred C57BL, Electrophysiology, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, chemistry, Female, Polyunsaturated fatty acids, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Causal link, business, Neuroscience, 030217 neurology & neurosurgery, medicine.drug, Polyunsaturated fatty acid
Abstract

International audience; Reward-processing impairment is a common symptomatic dimension of several psychiatric disorders. However, whether the underlying pathological mechanisms are common is unknown. Herein, we asked if the decrease in the n-3 polyunsaturated fatty acid (PUFA) lipid species, consistently described in these pathologies, could underlie reward-processing deficits. We show that reduced n-3 PUFA biostatus in mice leads to selective motivational impairments. Electrophysiological recordings revealed increased collateral inhibition of dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) onto dopamine D1 receptor-expressing MSNs in the nucleus accumbens, a main brain region for the modulation of motivation. Strikingly, transgenically preventing n-3 PUFA deficiency selectively in D2-expressing neurons normalizes MSN collateral inhibition and enhances motivation. These results constitute the first demonstration of a causal link between a behavioral deficit and n-3 PUFA decrease in a discrete neuronal population and suggest that lower n-3 PUFA biostatus in psychopathologies could participate in the etiology of reward-related symptoms.

Published
2020

8. Cholesterol metabolism and glaucoma: Modulation of Muller cell membrane organization by 24S-hydroxycholesterol

Author

Ségolène Gambert, Elodie Masson, Arthur Vannier, Géraldine Lucchi, Arthur Ferrerro, Delphine Pecqueur, Clément Gendrault, Laurent Leclere, Méline Lachot, Lucy Martine, Stéphane Grégoire, Caroline Truntzer, Alain M. Bron, Elise Léger-Charnay, Pierre-Henry Gabrielle, Catherine Creuzot-Garcher, Lionel Bretillon, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), OEil, nutrition et signalisation cellulaire [CSGA], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Plate-forme Protéomique CLIPP - Clinical and Innovation Proteomic Platform [Dijon] (CLIPP), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM)-Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Plate-forme Protéomique CLIPP - Clinical and Innovation Proteomic Platform [Dijon] ( CLIPP ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies ( FEMTO-ST ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ) -Université de Technologie de Belfort-Montbeliard ( UTBM ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ) -Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] ( ICMUB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), and Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Cell, Ependymoglial Cells, Biochemistry, Retinal ganglion, Cell membrane, 24S-hydroxycholesterol, 03 medical and health sciences, chemistry.chemical_compound, Muller cells, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Animals, Rats, Long-Evans, Molecular Biology, Lipid raft, Cells, Cultured, Retina, Raft microdomain, Organic Chemistry, Cell Membrane, Retinal, Glaucoma, Cell Biology, Hydroxycholesterols, Cell biology, Rats, 030104 developmental biology, medicine.anatomical_structure, Cholesterol, chemistry, Gliosis, lipids (amino acids, peptides, and proteins), sense organs, medicine.symptom, Sphingomyelin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Glaucoma is a progressive and irreversible blinding neuropathy that is characterized by the loss of retinal ganglion cells (RGCs). Muller Glial Cell (MGC) activation is induced in retinal gliosis. MGCs are the most numerous glial cells in the retina and one of their roles is to sustain cholesterol homeostasis. 24S-hydroxycholesterol (24S-OHC) is one of the form of cholesterol elimination from the retina and is overexpressed during glaucoma. The objective of this study was to determine whether 24S-OHC triggers MGC membrane dynamics involving lipid rafts and contributes to gliosis at early and late time points. A proteomic analysis was carried out by nanoLC-MS/MS in raft and non-raft fractions from MGCs after treatment with 24S-OHC (10μM). The expression of structural and functional proteins was further analyzed by Western-blotting, as well as the levels of GM3 ganglioside by LC-MS. Cholesterol, sphingomyelin, saturated fatty acids and ganglioside GM3 are enriched in the rafts fractions in MGCs. Caveolin-1, flotillin-1, connexin-30 and -43 are localized in the MGCs rafts. Proteins implicated in adhesion or oxidative stress pathways in raft fractions were up and down-regulated by the treatment. Our data showed that 24S-OHC induced early changes in protein distribution in raft microdomains; however, further studies are needed to better characterize the surrounded mechanisms.

Published
2017

9. Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N

Author

El Mostafa Karym, Meryam Debbabi, Michel Prost, Maryem Bezine, Randa Sghaier, Anne Vejux, Gérard Lizard, Stéphane Grégoire, Wiem Meddeb, Philippe Durand, Lucy Martine, Amira Zarrouk, Lionel Bretillon, Boubker Nasser, Thomas Nury, Asmaa Badreddine, Thibault Moreau, Mustapha Cherkaoui-Malki, Emmanuelle Prost-Camus, Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Hassan 1er [Settat], Université de Monastir - University of Monastir (UM), Faculté de médecine de Sousse [Ibn EL Jazzar], Institut préparatoire aux études scientifiques et techniques [La Marsa] (IPEST), Université de Sousse, Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Laboratoire de Recherche Appliquée Spiral [Bourgogne] (LARA SPIRAL), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), This work was supported by grants from: University of Bourgogne (Dijon, France), University of Monastir (Monastir, Tunisia), Aides et Services à Domicile (ASSAD) (Louhans, France) and the Association Bourguignonne pour les Aplications en Sciences de l’Information en Médecine (ABASIM, Dijon, France). This work was supported by the Action Intégrée of the Comité Mixte Inter-Universitaire Franco-Marocain (CMIFM, MA/14/310) from the Projet Hubert Curien (PHC) Volubilis/Toubkal program, the Ministère de l’Enseignement Supérieur and the Centre National Pour la Recherche Scientifique et Technique (CNRST, Morocco), the projet PPR from the (CNRST, Morocco), the Ministère des Affaires Etrangères, the Conseil Régional de Bourgogne, and the University of Bourgogne. We also thank Philip Bastable for English corrections (University Hospital, Dijon, France)., Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique ( Bio-PeroxIL ), Université de Bourgogne ( UB ), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] ( BIO-PEROXIL ), Université de Bourgogne ( UB ) -Université Bourgogne Franche-Comté ( UBFC ), Nutrition, Aliments Fonctionnels et Santé Vasculaire, Université de Monastir ( UM ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Recherche Appliquée Spiral [Bourgogne] ( LARA SPIRAL ), Modélisation mathématique et numérique ( M2N ), Conservatoire National des Arts et Métiers [CNAM] : EA7340, UMR 6578 : Adaptabilité Biologique et Culturelle ( UAABC ), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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 de Biochimie et Neurosciences [Settat, Maroc], Faculté des Sciences et Techniques de Settat-Université Hassan I [Maroc], University of Bourgogne (Dijon, France) University of Monastir (Monastir, Tunisia) Aides et Services a Domicile (ASSAD) (Louhans, France) Association Bourguignonne pour les Aplications en Sciences de l'Information en Medecine (ABASIM, Dijon, France) Action Integree of the Comite Mixte Inter-Universitaire Franco-Marocain (CMIFM) from the Projet Hubert Curien (PHC) Volubilis/Toubkal program MA/14/310 Ministere de l'Enseignement Superieur Centre National Pour la Recherche Scientifique et Technique (CNRST, Morocco) projet PPR from the (CNRST, Morocco) Ministere des Affaires Etrangeres Conseil Regional de Bourgogne University of Bourgogne, and Lizard, Gérard

Subjects
MESH: Plant Oils/pharmacology, Antioxidant, argan oil, extra virgin olive oil, alpha-tocopherol, 7-ketocholesterol, mitochondria, lysosome, peroxisome, oxiapoptophagy, 158N murine, oligodendrocytes, assay interference compounds, polyunsaturated fatty-acids, smooth-muscle-cells, blood-brain-barrier, pear seed oil, alzheimers-disease, docosahexaenoic acid, mediterranean diet, multiple-sclerosis, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Antioxidants/pharmacology, Apoptosis, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Antioxidants, MESH: Lipid Peroxidation, lcsh:Chemistry, Lipid peroxidation, Mice, MESH: Oligodendroglia/drug effects, MESH: Animals, MESH: Oxidative Stress/drug effects, lcsh:QH301-705.5, Spectroscopy, chemistry.chemical_classification, General Medicine, régime méditerranéen, α-tocopherol, 158N murine oligodendrocytes, 3. Good health, maladie d'alzheimer, mitochondrie, MESH: Lysosomes/drug effects, Article, Inorganic Chemistry, 03 medical and health sciences, food, huile d'olive vierge, acide gras polyinsaturé, Food and Nutrition, sclérose en plaques, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, tocopherol, huile d'argan, MESH: Cell Line, Tyrosol, MESH: Ketocholesterols/toxicity, 030104 developmental biology, chemistry, MESH: Mitochondria/drug effects, barrière hematoencephalique, Lipid Peroxidation, 0301 basic medicine, Argan oil, medicine.disease_cause, chemistry.chemical_compound, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Ketocholesterols, 2. Zero hunger, MESH: Peroxisomes/drug effects, Computer Science Applications, Oligodendroglia, Neuroprotective Agents, Biochemistry, Docosahexaenoic acid, Alimentation et Nutrition, Polyunsaturated fatty acid, food.ingredient, MESH: Apoptosis/drug effects, Context (language use), Biology, Catalysis, Cell Line, Peroxisomes, medicine, Animals, Plant Oils, Physical and Theoretical Chemistry, MESH: alpha-Tocopherol/pharmacology, MESH: Mice, MESH: Neuroprotective Agents/pharmacology, Organic Chemistry, Oxidative Stress, lcsh:Biology (General), lcsh:QD1-999, Lysosomes, Oxidative stress
Abstract

PMCID: PMC5666899; International audience; Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects. These compounds may be either natural or synthetic molecules or mixtures of molecules such as oils. In this context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were determined by different chromatographic techniques; and (ii) their anti-oxidant and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25-50 mu M; 24 h) without and with argan oil (0.1% v/v) or -tocopherol (400 mu M, positive control) were evaluated with complementary techniques of cellular and molecular biology. Among the unsaturated fatty acids present in argan oils, oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0). Several phytosterols were found, mainly schottenol and spinasterol (specific to argan oil), cycloartenol, beta-amyrin and citrostadienol alpha- and gamma-tocopherols were also present. Tyrosol and protocatechic acid were the only polyphenols detected. Argan and extra virgin olive oils have many compounds in common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and extra virgin olive oils have anti-oxidant properties. Argan oils were able to attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell growth inhibition, increased plasma membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood-brain barrier.

Published
2017

10. Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

Author

Sofien Ben Ammou, Anne Vejux, Meryam Debbabi, Stéphane Grégoire, Philippe Durand, Nadia Mekahli, Emmanuelle Camus, Lionel Bretillon, Amira Zarrouk, Maryem Bezine, Lucy Martine, Aymen Jabrane, Gérard Lizard, Mohamed Hammami, Thibault Moreau, Randa Sghaier, Michel Prost, Thomas Nury, Lizard, Gérard, Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique (Bio-PeroxIL), Université de Bourgogne (UB), Université de Monastir - University of Monastir (UM), Faculté de médecine de Sousse [Ibn EL Jazzar], Université Tunis El Manar (UTM), Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), OEil, nutrition et signalisation cellulaire [CSGA], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Recherche Appliquée Spiral [Bourgogne] (LARA SPIRAL), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Universitaire Sahloul (CHU Sahloul), Université de Bourgogne (Dijon, France), Université de Monastir (Monastir, Tunisia), Université El Manar (Tunis, Tunisia), ASSAD (Louhans, France), Nopal Nutra (Dijon, France), and Departments of Neurology (University Hospital, Dijon, France) and (University Hospital, Sousse, Tunisia)., Université de Tunis El Manar (UTM), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique ( Bio-PeroxIL ), Université de Bourgogne ( UB ), Nutrition, Aliments Fonctionnels et Santé Vasculaire, Université de Monastir ( UM ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Recherche Appliquée Spiral [Bourgogne] ( LARA SPIRAL ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), and University Hospital of Sahloul

Subjects
0301 basic medicine, Antioxidant, Organes des sens, medicine.medical_treatment, Trolox, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, alpha-Tocopherol, MESH: Antioxidants/pharmacology, MESH: Peroxisomes/drug effects, Antioxidants, biochimie métabolique, lcsh:Chemistry, Lipid peroxidation, Mice, chemistry.chemical_compound, peroxisome, MESH: Animals, lcsh:QH301-705.5, Ketocholesterols, Spectroscopy, Membrane Potential, Mitochondrial, α-tocopherol, γ-tocopherol, oleic acid, mitochondria, murine microglial BV-2 cells, peroxydation lipidique, Neurodegeneration, General Medicine, Peroxisome, 3. Good health, Computer Science Applications, MESH: Membrane Potential, Mitochondrial/drug effects, Biochemistry, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Microglia/metabolism, Alimentation et Nutrition, Microglia, MESH: Mitochondria/pathology, MESH: Mitochondria/drug effects, acide oléique, Programmed cell death, MESH: gamma-Tocopherol/pharmacology, Sensory Organs, Médecine humaine et pathologie, Biology, Article, Catalysis, Cell Line, Inorganic Chemistry, 03 medical and health sciences, MESH: Oleic Acid/pharmacology, Peroxisomes, medicine, Animals, Food and Nutrition, Propidium iodide, Physical and Theoretical Chemistry, Olive Oil, Molecular Biology, MESH: Mice, MESH: Peroxisomes/pathology, maladie neurodégénérative, MESH: Microglia/drug effects, gamma-Tocopherol, MESH: Ketocholesterols/pharmacology, Organic Chemistry, Neurosciences, gène mitochondrial, medicine.disease, MESH: Olive Oil/pharmacology, MESH: Cell Line, Oleic acid, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, chemistry, Neurons and Cognition, Human health and pathology, MESH: alpha-Tocopherol/pharmacology
Abstract

Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of alpha- and gamma-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only alpha-, and gamma-tocopherol, and Trolox had antioxidant properties. However, only alpha-tocopherol, gamma-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, alpha-and gamma-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal beta-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

Published
2016
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11. Diversity of Sterol Composition in Tunisian Pistacia lentiscus Seed Oil

Author

Lucy Martine, Olivier Berdeaux, Arbia Labidi, Abdelhamid Khaldi, Mohamed Larbi Khouja, Faten Mezni, Institut National de Recherche en Génie Rural Eaux et Forêts (INRGREF), Ecole Nationale du Génie Rural, des Eaux et des Forêts (ENGREF), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), IRDC-Canada 105568-006, Institut National de Recherche en Génie Rural Eaux et Forêts ( INRGREF ), Ecole Nationale du Génie Rural, des Eaux et des Forêts ( ENGREF ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), and Ecole Nationale du Génie Rural, des Eaux et des Forêts (ENGREF)-Institution de la Recherche et de l'Enseignement Supérieur Agricoles [Tunis] (IRESA)

Subjects
0301 basic medicine, Mediterranean climate, Chromatography, Gas, Tunisia, sunflower, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Molecular Conformation, phytosterols, Bioengineering, netherlands, cancer risk, Biochemistry, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, foods, Plant Oils, Molecular Biology, Diversity, 030109 nutrition & dietetics, biology, Phytosterol, 04 agricultural and veterinary sciences, General Chemistry, General Medicine, fruit, biology.organism_classification, 040401 food science, Sunflower, Sterol, Horticulture, Sterols, chemistry, Pistacia lentiscus, Pistacia, Seeds, Cycloartenol, Molecular Medicine, Composition (visual arts), lipids (amino acids, peptides, and proteins), Gas chromatography, accumulation, diet, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Seed oil
Abstract

International audience; Pistacia lentiscus L. seed oil is used in some Mediterranean forest area for culinary and medicinal purposes. In this study, we aim to examine, for the first time, the effect of growing area on sterol content of Pistacia lentiscus seed oil. Fruits were harvested from 13 different sites located in northern and central Tunisia. Gas chromatography-flame-ionization detection (GC-FID) was used to quantify sterols and gas chromatography/mass spectrometry (GC/MS) was used to identify them. The major sterol identified was b-sitosterol with a value ranging from 854.12 to 1224.09 mg/kg of oil, thus making up more than 54% of the total sterols. The other two main sterols were cycloartenol (11%) and 24-methylene-cycloartenol (5%). Statistical results revealed that growing location significantly (P < 0.001) affected phytosterol levels in these oils.

Published
2016

12. Plasmatic Ganglioside Profile and Age-Related Macular Degeneration

Author

Elodie Masson, Catherine Creuzot-Garcher, Olivier Berdeaux, Lionel Bretillon, Estelle Sibille, Denis Dossarps, Alain M. Bron, Lucy Martine, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Direction de la recherche clinique (Centre Hospitalier Universitaire de Dijon) Universite de Bourgogne Franche-Comte INRA Conseil Regional de Bourgogne FEDER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS )

Subjects
0301 basic medicine, Nervous system, Male, genetic structures, Severity of Illness Index, Ceramide, chemistry.chemical_compound, Macular Degeneration, Plasma, Gangliosides, liquid-chromatography, Glycosphingolipid, pathogenesis, General Medicine, Prognosis, Lipids, Sensory Systems, medicine.anatomical_structure, Biochemistry, Female, lipids (amino acids, peptides, and proteins), gd2 ganglioside, Tomography, Optical Coherence, medicine.medical_specialty, Retina, quantitative-analysis, 03 medical and health sciences, Cellular and Molecular Neuroscience, neuroblastoma, Internal medicine, Age related, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, cancer, Aged, Retrospective Studies, Ganglioside, Age-related macular degeneration, Case-control study, Macular degeneration, mass-spectrometry, medicine.disease, eye diseases, sandhoff, Ophthalmology, 030104 developmental biology, Endocrinology, chemistry, sense organs, Liquid chromatography coupled to mass spectrometry, serum, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Chromatography, Liquid
Abstract

Purpose: Gangliosides are glycosphingolipids that are particularly abundant in the nervous system, including the retina. However, their precise role in this tissue and its pathologies remain poorly understood. The objective of the present study was to characterize the ganglioside profile of human plasma and to determine whether it is affected in age-related macular degeneration (AMD). Methods: Eighty-three subjects were included: control subjects (n = 25), atrophic AMD patients (n = 27) and exudative AMD patients (n = 31). For each subject, gangliosides were extracted from plasma and analyzed by liquid chromatography coupled to mass spectrometry. Results: GM3 appeared to be by far the major ganglioside of human plasma, associated with GD3. No specific ganglioside class was detected in the plasma of AMD patients. Fourteen molecular species of GM3 and 9 species of GD3, accounting for the variability of the ceramide moiety of the ganglioside molecule, were identified and characterized. Analyses revealed no significant differences in the proportion of these species between control, atrophic and exudative AMD patient groups. Total GM3 levels did not differ either. Conclusion: Although gangliosides are considered important for the retina's structure and function, it seems that circulating gangliosides are not associated with the retinal damage occurring during the course of AMD.

Published
2016

13. Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities

Author

Olivier Berdeaux, Estelle Sibille, Elodie Masson, Lucy Martine, Gilles Thuret, Zhiguo He, Lionel Bretillon, Catherine Creuzot-Garcher, Alain M. Bron, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), OEil, nutrition et signalisation cellulaire [CSGA], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biologie, Ingénierie et Imagerie de la Greffe de Cornée (EA 2521, JE2521, IFR143), Université Jean Monnet [Saint-Étienne] (UJM), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Regional Council of Burgundy French National Institute for Research on Agronomy (INRA) European Regional Development Fund (FEDER), Masson, Elodie, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Biologie, Ingénierie et Imagerie de la Greffe de Cornée ( EA 2521, JE2521, IFR143 ), Université Jean Monnet [Saint-Étienne] ( UJM ), Institut Universitaire de France ( IUF ), and Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. )

Subjects
Male, 0301 basic medicine, Nervous system, Organes des sens, Physiology, Cell Membranes, gm1, lcsh:Medicine, Structural diversity, functional-role, Biochemistry, Mass Spectrometry, Plasma, chemistry.chemical_compound, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Gangliosides, Medicine and Health Sciences, tandem mass-spectrometry, lcsh:Science, Multidisciplinary, Spectrometers, glycosphingolipids, bovine, Fatty Acids, Biologie du développement, Brain, Hematology, Lipids, Development Biology, Body Fluids, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Cell biology, Blood, medicine.anatomical_structure, Organ Specificity, [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Peripheral nervous system, Engineering and Technology, Female, Anatomy, Cellular Structures and Organelles, Signal transduction, Mass Spectrometers, Research Article, signal-transduction, Ceramide, rat retina, Ocular Anatomy, rétine, Sensory Organs, Equipment, Biology, Retina, Blood Plasma, rafts, personne âgée, 03 medical and health sciences, Ocular System, medicine, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, système nerveux, Measurement Equipment, ceramide composition, Ganglioside, lcsh:R, Neurosciences, Biology and Life Sciences, Optic Nerve, Cell Biology, Functional integrity, 030104 developmental biology, chemistry, Neurons and Cognition, major gangliosides, Immunology, lcsh:Q, Chromatography, Liquid
Abstract

International audience; Gangliosides make a wide family of glycosphingolipids, highly heterogeneous in both the ceramide moiety and the oligosaccharide chain. While ubiquitously expressed in mammalian tissues, they are particularly abundant in the brain and the peripheral nervous system. Gangliosides are known to play a crucial role in the development, maintenance and functional integrity of the nervous system. However, the expression and roles of gangliosides in the retina, although often considered as a window on the brain, has been far less studied. We performed an in-depth analysis of gangliosides of the human retina, especially using powerful LC/MS methods. We compared the pattern of ganglioside classes and ceramide molecular species of this tissue with other ocular structures and with brain and plasma in elderly human individuals. About a hundred of ganglioside molecular species among 15 distinct classes were detected illustrating the huge structural diversity of these compounds. The retina exhibited a very diverse ganglioside profile and shared several common features with the brain (prominence of tetraosylgangliosides, abundance of d20:1 long chain base and 18:0 fatty acid...). However, the retina stood out with the specific expression of GD3, GT3 and AcGT3, which further presented a peculiar molecular species distribution. The unique ganglioside pattern we observed in the human retina suggests that these ganglioside species play a specific role in the structure and function of this tissue. This lipidomic study, by highlighting retina specific ganglioside species, opens up novel research directions for a better understanding of the biological role of gangliosides in the retina.

Published
2016

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