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1. Fecal Metabolic Profiling of Breast Cancer Patients during Neoadjuvant Chemotherapy Reveals Potential Biomarkers

Author

Nessrine Souai, Laetitia Shintu, Fabrice Tranchida, Amor Mosbah, Farhat Ben Ayed, Henda Raies, Ameur Cherif, Sonia Mezrioui, Oumaima Zidi, Soumaya Kouidhi, Amel Mezlini, Jean-Marc Sabatier, Institut de neurophysiopathologie (INP), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oncology, Male, Proton Magnetic Resonance Spectroscopy, Pharmaceutical Science, Gut flora, medicine.disease_cause, Analytical Chemistry, Feces, 0302 clinical medicine, MESH: Least-Squares Analysis, Drug Discovery, MESH: Metabolomics, metabolites, 0303 health sciences, MESH: Proton Magnetic Resonance Spectroscopy, Principal Component Analysis, MESH: Middle Aged, biology, MESH: Feces, Discriminant Analysis, dysbiosis, Middle Aged, metabolomics, Neoadjuvant Therapy, 3. Good health, Chemistry (miscellaneous), 030220 oncology & carcinogenesis, Metabolome, Molecular Medicine, Female, MESH: Biomarkers, Tumor, MESH: Metabolome, Metabolic Networks and Pathways, medicine.medical_specialty, MESH: Neoadjuvant Therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Article, lcsh:QD241-441, 03 medical and health sciences, Breast cancer, Metabolomics, lcsh:Organic chemistry, Internal medicine, medicine, MESH: Carbon-13 Magnetic Resonance Spectroscopy, Biomarkers, Tumor, Humans, Physical and Theoretical Chemistry, Carbon-13 Magnetic Resonance Spectroscopy, Least-Squares Analysis, MESH: Fatty Acids, Volatile, 030304 developmental biology, MESH: Principal Component Analysis, MESH: Humans, gut microbiota, business.industry, breast cancer (BC), Organic Chemistry, Cancer, MESH: Discriminant Analysis, biomarkers, MESH: ROC Curve, Omics, medicine.disease, biology.organism_classification, Fatty Acids, Volatile, MESH: Male, ROC Curve, MESH: Metabolic Networks and Pathways, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, Carcinogenesis, Dysbiosis, MESH: Female, MESH: Breast Neoplasms
Abstract

International audience; Breast cancer (BC) is the most common form of cancer among women worldwide. Despite the huge advancements in its treatment, the exact etiology of breast cancer still remains unresolved. There is an increasing interest in the role of the gut microbiome in modulating the anti-cancer therapeutic response. It seems that alteration of the microbiome-derived metabolome potentially promotes carcinogenesis. Taken together, metabolomics has arisen as a fascinating new omics field to screen promising metabolic biomarkers. In this study, fecal metabolite profiling was performed using NMR spectroscopy, to identify potential biomarker candidates that can predict response to neoadjuvant chemotherapy (NAC) for breast cancer. Metabolic profiles of feces from patients (n = 8) following chemotherapy treatment cycles were studied. Interestingly, amino acids were found to be upregulated, while lactate and fumaric acid were downregulated in patients under the second and third cycles compared with patients before treatment. Furthermore, short-chain fatty acids (SCFAs) were significantly differentiated between the studied groups. These results strongly suggest that chemotherapy treatment plays a key role in modulating the fecal metabolomic profile of BC patients. In conclusion, we demonstrate the feasibility of identifying specific fecal metabolic profiles reflecting biochemical changes that occur during the chemotherapy treatment. These data give an interesting insight that may complement and improve clinical tools for BC monitoring.

Published
2021

2. Targeting Mitochondrial Complex I Overcomes Chemoresistance in High OXPHOS Pancreatic Cancer

Author

Fabrice Tranchida, Odile Gayet, Alice Carrier, Gabriela Reyes-Castellanos, Laurie Cormareche, Tristan Gicquel, Juan L. Iovanna, Samir Dou, Nelson Dusetti, Eddy Pasquier, Laurence Borge, Binta Diémé, Laetitia Shintu, Julie Garcia, Rawand Masoud, Abdessamad El Kaoutari, Nadine Abdel Hadi, Sophie Lac, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, is work was supported by InstitutNational de la Sante ́et de la Recherche Me ́dicale, Centre National de la Re-cherche Scientifique, Institut National Du Cancer (INCa), Fondation ARCpour la Recherche sur le Cancer (PJA 20151203544), La Ligue Nationalecontre le Cancer (LNCC), DGOS (labelization SIRIC), Fondation Amidex, andFondation de France. This work also benefited from grants from Cancerop^oleProvence-Alpes-C^ote d’Azur (PACA) and Fe ́de ́ration GEFLUC for the acquisi-tion of the Seahorse XFe24 device., Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), PFEM, MetaboHUB, CARRIER, Alice, Plateforme Exploration du Métabolisme-MetaboHUB (PFEM-MetaboHUB), and Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)

Subjects
Male, endocrine system diseases, medicine.medical_treatment, [SDV]Life Sciences [q-bio], pancreatic cancer, cancer metabolism, Mitochondrion, Phenformin, Deoxycytidine, Oxidative Phosphorylation, chemistry.chemical_compound, Mice, 0302 clinical medicine, 0303 health sciences, personalized medicine, OXPHOS, 3. Good health, Mitochondria, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, PC-3 Cells, Female, Mitochondrial Complex I, medicine.drug, Carcinoma, Pancreatic Ductal, energetic metabolism, Cell Respiration, Mice, Nude, Oxidative phosphorylation, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Pancreatic cancer, Cell Line, Tumor, medicine, Animals, Humans, therapeutic strategy, 030304 developmental biology, Cell Proliferation, Chemotherapy, Electron Transport Complex I, business.industry, metabolic heterogeneity, medicine.disease, mitochondrial Complex I, Xenograft Model Antitumor Assays, Gemcitabine, digestive system diseases, Mice, Inbred C57BL, Pancreatic Neoplasms, chemistry, Drug Resistance, Neoplasm, Cancer research, Personalized medicine, business
Abstract

Summary Mitochondrial respiration (oxidative phosphorylation, OXPHOS) is an emerging target in currently refractory cancers such as pancreatic ductal adenocarcinoma (PDAC). However, the variability of energetic metabolic adaptations between PDAC patients has not been assessed in functional investigations. In this work, we demonstrate that OXPHOS rates are highly heterogeneous between patient tumors, and that high OXPHOS tumors are enriched in mitochondrial respiratory complex I at protein and mRNA levels. Therefore, we treated PDAC cells with phenformin (complex I inhibitor) in combination with standard chemotherapy (gemcitabine), showing that this treatment is synergistic specifically in high OXPHOS cells. Furthermore, phenformin cooperates with gemcitabine in high OXPHOS tumors in two orthotopic mouse models (xenografts and syngeneic allografts). In conclusion, this work proposes a strategy to identify PDAC patients likely to respond to the targeting of mitochondrial energetic metabolism in combination with chemotherapy, and that phenformin should be clinically tested in appropriate PDAC patient subpopulations., Graphical Abstract, Highlights Pancreatic ductal adenocarcinoma (PDAC) displays OXPHOS heterogeneity High OXPHOS PDAC tumors are enriched in mitochondrial respiratory complex I Complex I inhibitor phenformin synergizes with chemotherapy in high OXPHOS cells Phenformin cooperates with gemcitabine antitumoral activity in high OXPHOS tumors, Masoud et al. reveal that pancreatic cancer patients can be stratified according to their mitochondrial oxidative phosphorylation (OXPHOS) activity and to the expression of mitochondrial respiratory complex I. Targeting mitochondrial respiration with the complex I inhibitor phenformin cooperates with gemcitabine to eradicate high OXPHOS pancreatic cancer cells.

Published
2020

3. Hepatic metabolic effects of Curcuma longa extract supplement in high-fructose and saturated fat fed rats

Author

Fabrice Tranchida, Zo Rakotoniaina, Laetitia Shintu, Léopold Tchiakpe, Valérie Deyris, Mehdi Yemloul, Pierre Stocker, Nicolas Vidal, Odile Rimet, Abel Hiol, Stefano Caldarelli, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Qualisud - Pôle de La Réunion (Qualisud Réunion), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Male, Science, Proton Magnetic Resonance Spectroscopy, Fructose, Diet, High-Fat, Article, Choline, Rats, Sprague-Dawley, Curcuma, Malondialdehyde, Animals, Least-Squares Analysis, Triglycerides, Plant Extracts, Fatty Acids, Discriminant Analysis, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Glutathione, Betaine, Liver, Dietary Supplements, Multivariate Analysis, Medicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; The metabolic effects of an oral supplementation with a Curcuma longa extract, at a dose nutritionally relevant with common human use, on hepatic metabolism in rats fed a high fructose and saturated fatty acid (HFS) diet was evaluated. High-resolution magic-angle spinning NMR and GC/MS in combination with multivariate analysis have been employed to characterize the NMR metabolite profiles and fatty acid composition of liver tissue respectively. The results showed a clear discrimination between HFS groups and controls involving metabolites such as glucose, glycogen, amino acids, acetate, choline, lysophosphatidylcholine, phosphatidylethanolamine, and β-hydroxybutyrate as well as an increase of MUFAs and a decrease of n-6 and n-3 PUFAs. Although the administration of CL did not counteract deleterious effects of the HFS diet, some metabolites, namely some n-6 PUFA and n-3 PUFA, and betaine were found to increase significantly in liver samples from rats having received extract of curcuma compared to those fed the HFS diet alone. This result suggests that curcuminoids may affect the transmethylation pathway and/or osmotic regulation. CL extract supplementation in rats appears to increase some of the natural defences preventing the development of fatty liver by acting on the choline metabolism to increase fat export from the liver.

Published
2017

4. Long-term high fructose and saturated fat diet affects plasma fatty acid profile in rats

Author

Léopold Tchiakpe, Zo Rakotoniaina, Valérie Deyris, Abel Hiol, Fabrice Tranchida, Olivier Ravion, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Université des Antilles et de la Guyane (UAG), Qualisud - Pôle de La Réunion (Qualisud Réunion), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)

Subjects
Male, medicine.medical_specialty, Linoleic acid, Saturated fat, Administration, Oral, 030209 endocrinology & metabolism, Fructose, General Biochemistry, Genetics and Molecular Biology, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dietary Sucrose, Plasma fatty acids, Internal medicine, medicine, Animals, Palmitoleic acid, General Pharmacology, Toxicology and Pharmaceutics, 030304 developmental biology, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, integumentary system, General Veterinary, Triglyceride, Fatty Acids, Fatty acid, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Metabolic syndrome, Dietary Fats, Rats, 3. Good health, Endocrinology, chemistry, Saturated fatty acid, Adaptive response, Arachidonic acid, High fructose and saturated fatty acid diet, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biotechnology
Abstract

International audience; As the consumption of fructose and saturated fatty acids (FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome, the aim of this study was to investigate the effects of a moderate (10 weeks) and a prolonged (30 weeks) high fructose and saturated fatty acid (HFS) diet on plasma FA composition in rats. The effects of a few weeks of HFS diet had already been described, but in this paper we tried to establish whether these effects persist or if they are modified after 10 or 30 weeks. We hypothesized that the plasma FA profile would be altered between 10 and 30 weeks of the HFS diet. Rats fed with either the HFS or a standard diet were tested after 10 weeks and again after 30 weeks. After 10 weeks of feeding, HFS-fed rats developed the metabolic syndrome, as manifested by an increase in fasting insulinemia, total cholesterol and triglyceride levels, as well as by impaired glucose tolerance. Furthermore, the plasma FA profile of the HFS group showed higher proportions of monounsaturated FAs like palmitoleic acid [16:1(n-7)] and oleic acid [18:1(n-9)], whereas the proportions of some polyunsaturated n-6 FAs, such as linoleic acid [18:2(n-6)] and arachidonic acid [20:4(n-6)], were lower than those in the control group. After 30 weeks of the HFS diet, we observed changes mainly in the levels of 16:1(n-7) (decreased) and 20:4(n-6) (increased). Together, our results suggest that an HFS diet could lead to an adaptive response of the plasma FA profile over time, in association with the development of the metabolic syndrome.

Published
2012

5. Metabolomic and Lipidomic Analysis of Serum Samples following Curcuma longa Extract Supplementation in High-Fructose and Saturated Fat Fed Rats

Author

Fabrice Tranchida, Zo Rakotoniaina, Stefano Caldarelli, Abel Hiol, Valérie Deyris, Laetitia Shintu, Léopold Tchiakpe, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Qualisud - Pôle de La Réunion (Qualisud Réunion), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Blood Glucose, Male, Magnetic Resonance Spectroscopy, Saturated fat, lcsh:Medicine, Antioxidants, Rats, Sprague-Dawley, chemistry.chemical_compound, 0302 clinical medicine, Blood serum, Insulin, Food science, lcsh:Science, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, biology, Fatty Acids, Lipids, Cholesterol, Biochemistry, Saturated fatty acid, Ketone bodies, Metabolic Networks and Pathways, Research Article, Polyunsaturated fatty acid, 030209 endocrinology & metabolism, Fructose, 03 medical and health sciences, Curcuma, Insulin resistance, medicine, Animals, Metabolomics, [CHIM]Chemical Sciences, Triglycerides, 030304 developmental biology, Fatty acid metabolism, Plant Extracts, lcsh:R, Lipid Metabolism, medicine.disease, biology.organism_classification, Dietary Fats, Diet, Rats, Oxidative Stress, chemistry, Dietary Supplements, lcsh:Q, High Fructose Corn Syrup, Blood Chemical Analysis
Abstract

International audience; We explored, using nuclear magnetic resonance (NMR) metabolomics and fatty acids profiling, the effects of a common nutritional complement, Curcuma longa, at a nutritionally relevant dose with human use, administered in conjunction with an unbalanced diet. Indeed, traditional food supplements have been long used to counter metabolic impairments induced by unbalanced diets. Here, rats were fed either a standard diet, a high level of fructose and saturated fatty acid (HFS) diet, a diet common to western countries and that certainly contributes to the epidemic of insulin resistance (IR) syndrome, or a HFS diet with a Curcuma longa extract (1% of curcuminoids in the extract) for ten weeks. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) on the serum NMR profiles and fatty acid composition (determined by GC/MS) showed a clear discrimination between HFS groups and controls. This discrimination involved metabolites such as glucose, amino acids, pyruvate, creatine, phosphocholine/glycerophosphocholine, ketone bodies and gly-coproteins as well as an increase of monounsaturated fatty acids (MUFAs) and a decrease of n-6 and n-3 polyunsaturated fatty acids (PUFAs). Although the administration of Curcuma longa did not prevent the observed increase of glucose, triglycerides, cholesterol and insulin levels, discriminating metabolites were observed between groups fed HFS alone or with addition of a Curcuma longa extract, namely some MUFA and n-3 PUFA, glycoproteins, glutamine, and methanol, suggesting that curcuminoids may act respectively on the fatty acid metabolism, the hexosamine biosynthesis pathway and alcohol oxidation. Curcuma longa extract supplementation appears to be beneficial in these metabolic pathways in rats. This metabolomic approach highlights important serum metabolites that could help in understanding further the metabolic mechanisms leading to IR.

Published
2015

6. Proteomic of lipid rafts in the exocrine pancreas from diet-induced obese rats

Author

Léopold Tchiakpe, Caroline Fasano, Abel Hiol, Danielle Comeau, Hang Thi Thu Nguyen, Fabrice Tranchida, Amine Adda Berkane, Abdul Waheed, El Hassan Ajandouz, Valérie Deyris, Louis Comeau, Cendrine Nicoletti, Véronique Desseaux, Physiologie neurovégétative - PNV (PNP), Université Paul Cézanne - Aix-Marseille 3-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), HIV Drug Resistance Program, Frederick National Laboratory for Cancer Research (FNLCR), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Qualisud - Pôle de La Réunion (Qualisud Réunion), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Université Paul Cézanne - Aix-Marseille 3, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), and ProdInra, Migration

Subjects
Male, Proteomics, OBESITE, [SDV]Life Sciences [q-bio], Biophysics, Biochemistry, Obese, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Membrane Microdomains, Rafts, BSDL, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, Molecular Biology, Lipid raft, Pancreas, 030304 developmental biology, 0303 health sciences, biology, Cholesterol, GP2, CHOLESTEROL, 030302 biochemistry & molecular biology, Cell Membrane, Proteins, Proteomic, Starch, Cell Biology, Immunogold labelling, Zymogen granule, Bile salt-dependent lipase, Pancreas, Exocrine, Rats, Diet, medicine.anatomical_structure, chemistry, Proteome, biology.protein, lipids (amino acids, peptides, and proteins), Diet-induced obese, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; In the present work, we induced obesity in rats with high-energy-starch diet and studied exocrine pancreas response. The zymogen granule (ZG) or purified plasma membrane (PM) from the exocrine pancreas was used for the isolation of the detergent-resistant membranes (DRMs). Based on high content of cholesterol, GM1, the bile salt dependent lipase (BSDL), and GP2 enrichment, the low-density fractions were defined as lipid rafts. Additionally, the rafts vesicles were determined by immunogold labeling with anti BSDL. By combining MALDI-TOF/MS and nano-LC ESI Q-TOF MS/MS proteomic identification we have selected 33 proteins from the lipid rafts which were classified into at least four functional families. Our data suggest that the acinar PM from the diet-induced obesity rats may be organized into lipid rafts, and characterization of rafts proteome can contribute to improve our understanding of food digestion under obesity. The exocrine pancreas is the major source of enzymes responsible for food digestion in the small intestine and its enzymatic adaptations to the diet composition has been reported [1]. Digestive enzymes in the acinar cells are stored in membrane vesicles called zymogen granules (ZGs). While the ZGs formation has been well-studied, their fusion to the PM and the regulation of digestive enzymes secretion from the apical acinar cells remain poorly understood. Our recent understanding of cell membranes suggest that the PM may be organized into heterogeneous functional microdomains and one of such microdomains known as lipid rafts are enriched in glycosphingolipids/ cholesterol and specific proteins [2]. The lipid rafts have been isolated from several mammalian cells, mostly by their resistance to non-ionic detergent extraction and buoyancy on gradient ultracentrifugation. Studies from our group and others have shown that these methods performed with caution remain to be one of efficient approach to isolate and study the compositions of lipid rafts [3]. It was reported that ZGs and GP2 interact with the lipid raft 0006-291X/$-see front matter Ó

Published
2007

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