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1. Transcriptome profiling reveals stress-responsive gene networks in cattle muscles

Author

Isabelle Cassar-Malek, Lise Pomiès, Anne de la Foye, Jérémy Tournayre, Céline Boby, and Jean-François Hocquette

Subjects
Pre slaugther stress, Cattle, Transcriptomics, Muscle response, Transcription factors, Medicine, Biology (General), QH301-705.5
Abstract

In meat-producing animals, preslaughter operations (e.g., transportation, mixing unfamiliar animals, food and water deprivation) may be a source of stress with detrimental effects on meat quality. The objective of this work was to study the effect of emotional and physical stress by comparing the transcriptomes of two muscles (M. longissimus thoracis, LT and M. semitendinosus, ST) in Normand cows exposed to stress (n = 16) vs. cows handled with limited stress (n = 16). Using a microarray, we showed that exposure to stress resulted in differentially expressed genes (DEGs) in both muscles (62 DEGs in LT and 32 DEGs in ST, of which eight were common transcription factors (TFs)). Promoter analysis of the DEGs showed that 25 cis transcriptional modules were overrepresented, of which nine were detected in both muscles. Molecular interaction networks of the DEGs targeted by the most represented cis modules helped identify common regulators and common targets involved in the response to stress. They provided elements showing that the transcriptional response to stress is likely to (i) be controlled by regulators of energy metabolism, factors involved in the response to hypoxia, and inflammatory cytokines; and (ii) initiate metabolic processes, angiogenesis, corticosteroid response, immune system processes, and satellite cell activation/quiescence. The results of this study demonstrate that exposure to stress induced a core response to stress in both muscles, including changes in the expression of TFs. These factors could relay the physiological adaptive response of cattle muscles to cope with emotional and physical stress. The study provides information to further understand the consequences of these molecular processes on meat quality and find strategies to attenuate them.

Published
2022
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2. Adipocyte/breast cancer cell crosstalk in obesity interferes with the anti-proliferative efficacy of tamoxifen.

Author

Lauriane Bougaret, Laetitia Delort, Hermine Billard, Camille Le Huede, Céline Boby, Anne De la Foye, Adrien Rossary, Ali Mojallal, Odile Damour, Céline Auxenfans, Marie Paule Vasson, and Florence Caldefie-Chezet

Subjects
Medicine, Science
Abstract

Obesity is a well-known risk factor of breast cancer in post-menopausal women that also correlates with a diminished therapeutic response. The influence of adipocytes and their secretome, i.e. adipokines, on the efficacy of hormone therapy has yet to be elucidated.We investigated, ex vivo, whether mature adipocytes, differentiated from adipose stem cells of normal-weight (MA20) or obese (MA30) women, and their secretions, were able to counteract the effects of tamoxifen (Tx) which is known to decrease neoplastic cell proliferation.In a tridimensional model and in a model of co-culture, the anti-proliferative effect of Tx on MCF-7 cancer cells was counteracted by MA30. These two models highlighted two different specific gene expression profiles for genes encoding cytokines or involved in angiogenesis based on the adipocyte microenvironment and the treatment. Thus it notably showed altered expression of genes such as TNFα that correlated with IL-6. In addition, leptin, IL-6 and TNFα, at concentrations reflecting plasma concentrations in obese patients, decreased the anti-proliferative efficacy of 4-hydroxytamoxifen (a major active metabolite of Tx).These findings bring insights on adipocytes and mammary cancer cell interactions in Tx therapy, particularly in overweight/obese people. Indeed, patient' adipokine status would give valuable information for developing individual strategies and avoid resistance to treatment.

Published
2018
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3. Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state.

Author

Dragan Milenkovic, Wim Vanden Berghe, Céline Boby, Christine Leroux, Ken Declerck, Katarzyna Szarc vel Szic, Karen Heyninck, Kris Laukens, Martin Bizet, Matthieu Defrance, Sarah Dedeurwaerder, Emilie Calonne, Francois Fuks, Guy Haegeman, Guido R M M Haenen, Aalt Bast, and Antje R Weseler

Subjects
Medicine, Science
Abstract

BackgroundIn a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation.Methodology/principal findingsGene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 864 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNF-α-stimulated endothelial cells. Nuclear factor kappa B (NF-κB) reporter gene assays confirmed that MOF decrease the activity of NF-κB. Strong inter-individual variability in the leukocytes' DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found.ConclusionOur study revealed that an 8 week daily supplementation with 200 mg MOF modulates the expression of genes associated with cardiovascular disease pathways without major changes of their DNA methylation state. However, strong inter-individual variation in leukocyte DNA methylation may obscure the subtle epigenetic response to dietary flavanols. Despite the lack of significant changes in DNA methylation, the modulation of gene expression appears to contribute to the observed vascular health effect of MOF in humans.

Published
2014
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4. Different miRNA contents between mammary epithelial cells and milk fat globules: a random or a targeted process?

Author

Nicolas Crapart, Christine Leroux, Gleidson Giordano Pinto de Carvalho, Claudia Bevilacqua, Céline Boby, Patrice Martin, Karol Pawlowski, Lenha Mobuchon, Yannick Faulconnier, Daiane Lago-Novais, Warsaw University of Life Sciences (SGGW), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade Federal da Bahia (UFBA), Génétique Animale et Biologie Intégrative (GABI), Université Paris-Saclay-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Excilone [Elancourt], PHASE (Physiologie Animale & Systemes d'Elevage) Department of INRA Brazilian Ministry of Science and Technology 'Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior' (CAPES) GISA meta-program of INRA (Ruminflame project), Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), Warsaw University of Life Sciences, and AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0301 basic medicine, Cell type, Mammary gland, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Lactating cow, Biology, Extracellular vesicles, 03 medical and health sciences, Mammary Glands, Animal, 0302 clinical medicine, microRNA, Genetics, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Glycoproteins, Milk fat, Mammary tissue, Epithelial Cells, MicroRNA, Lipid Droplets, General Medicine, Cell biology, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Nucleic acid, Cattle, Female, Glycolipids, Mammary epithelial cells
Abstract

International audience; MicroRNAs (miRNAs) are small noncoding RNAs present in milk-derived extracellular vesicles and milk fat globules(MFG). Nucleic acid content between the lactating mammary tissue (MT) and MFG are quite similar but discrepanciesexist in their miRNA content. Our objective was to identify the origin of these discrepancies, and to evaluate the existenceof a possible mechanism sorting miRNAs that will or will not be exported from the mammary epithelial cells (MECs) inbovine MFG. miR-125b-5p, miR-126-3p, miR-141-3p, and miR-204-5p, chosen on the basis of their abundance in the MT,were quantified using RT-qPCR in lactating cow MT, MFG, and laser capture-microdissected MECs. Two miRNAs (miR-125b-5p and miR-141-3p) were detected in the MT as well as in MFG and MECs. miR-204-5p was detected only in the MT,suggesting that it is very likely expressed in a cell type other than MECs. miR-126-3p was detected both in the MT and inMECs but not in MFG, suggesting a targeting mechanism for miRNAs in MECs. These results highlights differences inmiRNA content between MECs and MFG may be due to a possibly not random mechanism for loading MFG with miRNAcargos that could involve a variable distribution in MECs or a sorting mechanism.

Published
2020
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5. Circulating anthocyanin metabolites mediate vascular benefits of blueberries: insights from randomized controlled trials, metabolomics, and nutrigenomics

Author

Geoffrey Istas, Ana Rodriguez-Mateos, Christian Heiss, Charlotte E. Mills, Sergio Gómez-Alonso, Dragan Milenkovic, Céline Boby, Rodrigo P. Feliciano, Lisa Boschek, Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Department of Food and Nutritional Sciences, University College Cork (UCC), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Instituto Regional de Investigación Científica Aplicada (IRICA), Universidad de Castilla-La Mancha (UCLM), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Department of Internal Medicine, Division of Cardiovascular Medicine, University of California [Davis] (UC Davis), University of California-University of California, University of Surrey (UNIS), Surrey and Sussex Healthcare NHS Trust, Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), and University of California (UC)-University of California (UC)

Subjects
0301 basic medicine, Aging, Endothelium, Cellular differentiation, Blueberry Plants, Omics, 030204 cardiovascular system & hematology, Pharmacology, Peripheral blood mononuclear cell, Anthocyanins, 03 medical and health sciences, chemistry.chemical_compound, Nutrigenomics, 0302 clinical medicine, Immune system, Metabolomics, endothelial function, medicine, Animals, Humans, polyphenols, Randomized Controlled Trials as Topic, 2. Zero hunger, blueberries, business.industry, Polyphenols, Endothelial function, Blueberries, metabolomics, 3. Good health, omics, 030104 developmental biology, medicine.anatomical_structure, nutrition, chemistry, Cardiovascular Diseases, Anthocyanin, Models, Animal, Endothelium, Vascular, Geriatrics and Gerontology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Phytotherapy
Abstract

Potential health benefits of blueberries may be due to vascular effects of anthocyanins that predominantly circulate in blood as phenolic acid metabolites. We investigated which role blueberry anthocyanins and circulating metabolites play in mediating improvements in vascular function and explore potential mechanisms using metabolomics and nutrigenomics. Purified anthocyanins exerted a dose-dependent improvement of endothelial function in healthy humans, as measured by flow-mediated dilation. The effects were similar to those of wild blueberries containing similar amounts of anthocyanins, whereas control drinks containing fiber, minerals, or vitamins had no significant effect. Daily 1-month wild blueberry consumption increased flow-mediated dilation and lowered 24-hour ambulatory systolic blood pressure. Of the 63 anthocyanin plasma metabolites quantified, 14 and 21 correlated with acute and chronic flow-mediated dilation improvements, respectively. Injection of these metabolites improved flow-mediated dilation in mice. Daily wild blueberry consumption led to differential expression (>1.2-fold) of 608 genes and 3 microRNAs, with Mir-181c showing a 13-fold increase in peripheral blood mononuclear cells. Patterns of 13 metabolites were independent predictors of gene expression changes and pathway enrichment analysis revealed significantly modulated biological processes involved in cell adhesion, migration, immune response, and cell differentiation. Our results identify anthocyanin metabolites as major mediators of vascular bioactivities of blueberries and changes of cellular gene programs. Trial registration: NCT025208.

Published
2019
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6. Extruded linseed alone or in combination with fish oil modifies mammary gene expression profiles in lactating goats

Author

Christine Leroux, Céline Boby, Laurence Bernard, Jordann Domagalski, Yves Chilliard, Yannick Faulconnier, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
0301 basic medicine, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, medicine.medical_specialty, Peroxisome proliferator-activated receptor gamma, mammary gland, Protein metabolism, Biology, SF1-1100, Transcriptome, 03 medical and health sciences, chemistry.chemical_compound, Fish Oils, Mammary Glands, Animal, nutrigenomics, Flax, Internal medicine, Gene expression, medicine, caprine, Animals, Lactation, lipid supplementation, 2. Zero hunger, chemistry.chemical_classification, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Goats, Fatty Acids, 0402 animal and dairy science, Fatty acid, Lipid metabolism, AZGP1, 04 agricultural and veterinary sciences, Fish oil, 040201 dairy & animal science, Animal culture, Diet, 030104 developmental biology, Endocrinology, Gene Expression Regulation, chemistry, Cattle, Female, Animal Science and Zoology, transcriptome
Abstract

International audience; Nutrition is a major factor that regulates ruminant milk components, particularly its fatty acid (FA) composition, which is an important determinant of milk nutritional quality. In the mammary gland, milk component biosynthesis involves a large number of genes under nutritional regulation that are not well understood. Thus, the objective of the present study was to evaluate the effects of extruded linseeds (EL) alone or in combination with fish oil (ELFO) on goat mammary gene expression. In total, 14 goats were fed one of the following three diets: a natural grassland hay basal diet (CTRL) alone, CTRL supplemented with 530 g/day of EL, or 340 g/day of EL plus 39 g/day of fish oil (ELFO). Mammary secretory tissues were collected after slaughter on day 28, to determine the expression of 14 lipogenic genes and five lipogenic enzyme activities and transcriptomic profiles. The mRNA abundance decreased for SCD1 ( P

Published
2018
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7. Anthocyanins and their gut metabolites attenuate monocyte adhesion and transendothelial migration through nutrigenomic mechanisms regulating endothelial cell permeability

Author

Laurent-Emmanuel Monfoulet, Dragan Milenkovic, Céline Boby, Irene Krga, Sylvie Mercier, Radu Tamaian, Christine Morand, Marija Glibetić, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre of Research Excellence in Nutrition and Metabolism, University of Belgrade [Belgrade], R&D, National Institute of Research and Development for Cryogenic and Isotopic Technologies ICSI Rm. Valcea, Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Department of Internal Medicine, Division of Cardiovascular Mededicine, University of California [Davis] (UC Davis), University of California-University of California, University of California, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), University of California (UC)-University of California (UC), University of California (UC), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
0301 basic medicine, Cell signaling, fonction endothéliale, Gut metabolites, Biochemistry, Monocytes, MiRNA expression, mécanisme moléculaire, Capillary Permeability, Focal adhesion, Anthocyanins, 03 medical and health sciences, Nutrigenomics, Western blot, anthocyanine, Physiology (medical), Gene expression, Cell Adhesion, Human Umbilical Vein Endothelial Cells, medicine, Humans, Mode of action, Transcription factor, Transendothelial migration, medicine.diagnostic_test, Monocyte adhesion, Chemistry, Microarray analysis techniques, fungi, Transendothelial and Transepithelial Migration, food and beverages, Endothelial function, approche omique, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cell biology, Endothelial stem cell, carbohydrates (lipids), 030104 developmental biology, Cell signalling, rôle protecteur
Abstract

Cardioprotective effects of dietary anthocyanins are partly attributed to their ability to maintain endothelial function. However, the underlying cellular and molecular mechanisms of action are not fully understood. This study aimed to evaluate the effect of anthocyanins and their gut metabolites, at physiologically-relevant conditions, on endothelial cell (EC) function and decipher the underlying molecular mechanisms of action using integrated omics approaches. Primary EC were treated with a mixture of 0.1 mu M cyanidin-3-arabinoside, 0.1 mu M cyanidin-3-galactoside, 0.1 mu M cyanidin-3-glucoside, 0.1 mu M delphinidin-3-glucoside, 0.1 mu M peonidin-3-glucoside and 0.5 mu M 4-hydroxybenzaldehyde for 3 h or a mixture of gut metabolites: 0.2 mu M protocatechuic, 2 mu M vanillic, 1 mu M ferulic and 2 mu M hippuric acids for 18 h. Also, successive exposure of EC to both mixtures was performed to mimic anthocyanin pharmacokinetics following their intake. Inflammatory stress was induced using TNF alpha and monocytes added to assess adhesion and transmigration. Effects of these mixtures on gene, miRNA expression and their potential interaction with cell signalling were investigated. Anthocyanins and their gut metabolites significantly reduced monocyte adhesion and transendothelial migration. Gene expression analysis, using macroarrays, showed that tested compounds modulated the expression of genes involved in cell-cell adhesion, cytoskeleton organisation or focal adhesion. Bioinformatics analyses of gene expression data identified potential transcription factors involved in the observed nutrigenomic effects and signalling proteins regulating their activity. Molecular docking revealed cell signalling proteins to which these bioactives may bind to and potentially affect their activity and the activation of downstream signalling, effects that were in agreement with the results of Western blot analyses. Microarray analysis showed that anthocyanins and their gut metabolites affected miRNA expression in EC, especially those involved in regulation of EC permeability, contributing to the observed changes in EC function. Integration of these results revealed endothelial-protective properties of anthocyanins and their gut metabolites and deciphered new underlying multi-target and multi-layered mode of action.

Published
2018
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8. Substantial variability across individuals in the vascular and nutrigenomic response to an acute intake of curcumin: A randomizsed controlled trial

Author

Jean René Lusson, Bruno Pereira, Damien Richard, Andrzej Mazur, Claude Dubray, Céline Lambert, Nicolas Barber-Chamoux, Christine Morand, Véronique Habauzit, Marie-Anne Verny, Dragan Milenkovic, Céline Boby, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Délégation à la Recherche Clinique et à l'Innovation (DRCI), CHU Clermont-Ferrand, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre d’Investigation Clinique (CIC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Auvergne - Clermont-Ferrand I (UdA), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), service de Biostatistiques, DRCI, Centre Hospitalier Universitaire de Clermont-Ferrand, Unité Biostatistique, Institut de Recherche en Gestion et en Economie (IREGE), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Université d'Auvergne (Clermont Ferrand 1) (UdA), CIC 501, Université Clermont Auvergne (UCA), Biostatistics Unit (DRCI), Clinical pharmacology, Cardiologie, Hôpital Privé Jacques Cartier [Massy], UMR 766, Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Unité de Nutrition Humaine - Clermont Auvergne ( UNH ), Université Clermont Auvergne ( UCA ) -Institut national de la recherche agronomique [Auvergne/Rhône-Alpes] ( INRA Auvergne/Rhône-Alpes ), Délégation à la Recherche Clinique et à l'Innovation ( DRCI ), Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), Centre d’Investigation Clinique ( CIC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université d'Auvergne (Clermont Ferrand 1) ( UdA ), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), ARCA (Association de Recherche en Cardiologie d'Auvergne), Unité de Nutrition Humaine ( UNH ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université, Institut de Recherche en Gestion et en Economie ( IREGE ), Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ), Institut Pascal - Clermont Auvergne ( IP ), Sigma CLERMONT ( Sigma CLERMONT ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale, Centre de Recherche en Nutrition Humaine (CRNH). FRA., ProdInra, Archive Ouverte, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Pathology, Physiology, fonction endothéliale, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, 030232 urology & nephrology, Individuality, vascular system, 030204 cardiovascular system & hematology, nutrigenomic, law.invention, essai clinique, chemistry.chemical_compound, Nutrigenomics, 0302 clinical medicine, Randomized controlled trial, endothelial function, law, curcumin, nutrigénomique, ComputingMilieux_MISCELLANEOUS, Cross-Over Studies, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, blood pressure, food and beverages, clinical trial, Middle Aged, 3. Good health, Vasodilation, Population study, Female, Cardiology and Cardiovascular Medicine, mode d'apport, Biotechnology, medicine.medical_specialty, Subgroup analysis, Placebo, nutragenomics, random selection, inter-individual variability, 03 medical and health sciences, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Internal Medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, randomisation, 030109 nutrition & dietetics, business.industry, système vasculaire, Crossover study, Clinical trial, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, curcumine, Blood pressure, chemistry, Curcumin, Endothelium, Vascular, Transcriptome, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract

cope Curcumin exerts biological activities of interest in cardiovascular prevention. However, its vascular protective effect is still poorly investigated in humans. The present study aims to assess vasculat effect of an acute intake of curcumin and its nutrigenomic impact in circulating immune cells. Methods and results In a randomised, double-blind, crossover design, eighteen healthy smokers consumed a placebo or a 5-gram of curcumin. Before and two hours after the intake, vascular function measurements were performed by using flow-mediated dilation (FMD). In addition, endothelial function in the microcirculation and blood pressure were evaluated. Plasma curcumin concentrations and changes in gene expression in peripheral blood mononuclear cells (PBMC) were analysed. No significant effect of curcumin on FMD was observed when considering the entire study population, mainly due to a high inter-individual variability. A subgroup analysis according to the gender or the cardiovascular-risk score revealed a significant effect of curcumin on FMD in women and in subjects presenting lower cardiovascular risk. No change in gene expression was observed when data were analysed for all volunteers but changes in expression were observed when analyzed according to gender. Conclusions This clinical trial highlights that a substantial variability in efficacy of curcumin exists across individuals. This article is protected by copyright. All rights reserved

Published
2017
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9. Molecular regulation of high muscle mass in developing Blonde d'Aquitaine cattle fetuses

Author

Antonio Reverter, Brigitte Picard, Isabelle Cassar-Malek, Nicholas J. Hudson, Céline Boby, Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
0301 basic medicine, Gene isoform, medicine.medical_specialty, QH301-705.5, Science, [SDV]Life Sciences [q-bio], Myostatin, Biology, General Biochemistry, Genetics and Molecular Biology, genomic, race bovine blonde d'aquitaine, 03 medical and health sciences, Internal medicine, myostatine, Myosin, Gene expression, medicine, Biology (General), skeletal muscle, CSRP3, [ SDV ] Life Sciences [q-bio], Myogenesis, 0402 animal and dairy science, Skeletal muscle, muscle squelettique, 04 agricultural and veterinary sciences, Genomics, myogénèse, 040201 dairy & animal science, Molecular biology, mitochondria, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, voluntary muscle, mitochondrie, myostatin, fœtus amnion fetus yolk sac, biology.protein, MYH7, myogenesis, fœtus, General Agricultural and Biological Sciences, Research Article
Abstract

The Blonde d'Aquitaine (BA) is a French cattle breed with enhanced muscularity, partly attributable to a MSTN mutation. The BA m. Semitendinosus has a faster muscle fibre isoform phenotype comprising a higher proportion of fast type IIX fibres compared to age-matched Charolais (CH). To better understand the molecular network of modifications in BA compared to CH muscle, we assayed the transcriptomes of the m. Semitendinosus at 110, 180, 210 and 260 days postconception (dpc). We used a combination of differential expression (DE) and regulatory impact factors (RIF) to compare and contrast muscle gene expression between the breeds. Prominently developmentally regulated genes in both breeds reflected the replacement of embryonic myosin isoforms (MYL4, MYH3) with adult isoforms (MYH1) and the upregulation of mitochondrial metabolism (CKMT2, AGXT2L1) in preparation for birth. However, the transition to a fast, glycolytic muscle phenotype in the MSTN mutant BA is detectable through downregulation of various slow twitch subunits (TNNC1, MYH7, TPM3, CSRP3) beyond 210 dpc, and a small but consistent genome-wide reduction in mRNA encoding the mitoproteome. Across the breeds, NRIP2 is the regulatory gene possessing a network change most similar to that of MSTN., Summary: We explored the molecular basis of high muscle mass in Blonde d’Aquitaine cattle, and found that mRNA encoding slow fibres and mitochondrial proteins were downregulated in this breed.

Published
2017
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10. 0129 Liver transcriptome modifications by nutrient restriction in early lactation Holstein cows challenged with intramammary lipopolysaccharide

Author

K. Pawlowski, Yannick Faulconnier, Denys Durand, J.A.A. Pires, A. de la Foye, Céline Boby, and Christine Leroux

Subjects
medicine.medical_specialty, Lipopolysaccharide, General Medicine, Biology, Andrology, Transcriptome, chemistry.chemical_compound, Nutrient, medicine.anatomical_structure, Endocrinology, chemistry, Internal medicine, Lactation, Genetics, medicine, Animal Science and Zoology, Food Science
Published
2016
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11. 0131 Mammary gland transcriptome and proteome modifications by nutrient restriction in early lactation Holstein cows challenged with intramammary lipopolysaccharide

Author

Christine Leroux, K. Pawlowski, Yannick Faulconnier, A. de la Foye, J.A.A. Pires, Christophe Chambon, and Céline Boby

Subjects
medicine.medical_specialty, Lipopolysaccharide, Mammary gland, General Medicine, Biology, Transcriptome, Andrology, chemistry.chemical_compound, medicine.anatomical_structure, Endocrinology, Nutrient, chemistry, Internal medicine, Lactation, Proteome, Genetics, medicine, Animal Science and Zoology, Food Science
Published
2016
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12. Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways

Author

Christine Morand, Sylvain Claude, Jeremy P. E. Spencer, Dragan Milenkovic, Céline Boby, Nicolas Gérard, Ana Rodriguez-Mateos, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, University of Reading (UOR), European Project: 226588,EC:FP7:KBBE,FP7-KBBE-2008-2B,FLAVIOLA(2009), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)

Subjects
Flavonols, métabolite de flavanol, Sulfuric Acid Esters, Biology, p38 Mitogen-Activated Protein Kinases, Catechin, Monocytes, Focal adhesion, Transcriptome, Nutrigenomics, adhésion de monocyte, Cell Adhesion, Human Umbilical Vein Endothelial Cells, medicine, Humans, Phosphorylation, Cell adhesion, Tumor Necrosis Factor-alpha, Monocyte, Transcription Factor RelA, Endothelial Cells, Adhesion, Endothelial stem cell, medicine.anatomical_structure, Biochemistry, Tumor necrosis factor alpha, cellule endothéliale, Endothelium, Vascular, Signal transduction, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Signal Transduction, Transcription Factors, Food Science, Biotechnology, expression des gènes
Abstract

Scope Consumption of flavanol-rich foods is associated with an improvement in endothelial function. However, the specific biologically active flavanol metabolites involved in this benefit, as well as their molecular mechanisms of action have not been identified. The aim of this work was to examine the effect of plasma flavanol metabolites on adhesion of monocytes to TNF-α-activated endothelial cells and identify potential underlying mechanisms. Methods and results 4′-O-methyl(−)-epicatechin, 4′-O-methyl(−)-epicatechin-7-β-d-glucuronide, and (−)­epicatechin-4′-sulfate decreased the adhesion of monocytes to endothelial cells at physiologically relevant concentrations, from 0.2 to 1 μM. Transcriptomic studies showed that each of the flavanol metabolites affected the expression of different genes in endothelial cells. However, these genes are involved in the cellular processes that control adhesion and migration of monocytes to vascular endothelium, most notably those regulating cell adhesion, cell–cell junctions, focal adhesion, and cytoskeleton remodeling. Gene expression profiles obtained suggest lower monocyte recruitment, in agreement with results from cell adhesion assays. The nutrigenomic effect of metabolites seems to be mediated through their capacity to modulate phosphorylation of p65 and p38 cell-signaling proteins. Conclusion Our study provides findings into the molecular mechanisms by which plasma flavanol metabolites could be efficient to preserve vascular endothelium integrity in nutritionally relevant conditions.

Published
2014
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13. RhoB protects human keratinocytes from UVB-induced apoptosis through epidermal growth factor receptor signaling

Author

Anne Pradines, Marie Charveron, Isabelle Lajoie-Mazenc, Gilles Favre, Bruno Canguilhem, Céline Boby, and Caroline Baudouin

Subjects
Keratinocytes, DNA, Complementary, Time Factors, Transcription, Genetic, Cell Survival, Ultraviolet Rays, RHOB, Blotting, Western, Immunoblotting, Apoptosis, Enzyme-Linked Immunosorbent Assay, Biology, Biochemistry, Glycogen Synthase Kinase 3, Epidermal growth factor, RhoB GTP-Binding Protein, medicine, Phosphorylation, RNA Processing, Post-Transcriptional, RNA, Small Interfering, skin and connective tissue diseases, Promoter Regions, Genetic, rhoB GTP-Binding Protein, Molecular Biology, Protein kinase B, Cytoskeleton, Glycogen Synthase Kinase 3 beta, integumentary system, Cell Death, Reverse Transcriptase Polymerase Chain Reaction, Cell Biology, Cell biology, ErbB Receptors, medicine.anatomical_structure, UVB-induced apoptosis, Cancer research, RNA, Tumor promotion, Electrophoresis, Polyacrylamide Gel, Guanosine Triphosphate, Signal transduction, Keratinocyte, DNA Damage, Signal Transduction
Abstract

Next Section Abstract Exposure of the skin to UVB light results in the formation of DNA photolesions that can give rise to cell death, mutations, and the onset of carcinogenic events. Specific proteins are activated by UVB and then trigger signal transduction pathways that lead to cellular responses. An alteration of these signaling molecules is thought to be a fundamental event in tumor promotion by UVB irradiation. RhoB, encoding a small GTPase has been identified as a DNA damage-inducible gene. RhoB is involved in epidermal growth factor (EGF) receptor trafficking, cytoskeletal organization, cell transformation, and survival. We have analyzed the regulation of RhoB and elucidated its role in the cellular response of HaCaT keratinocytes to relevant environmental UVB irradiation. We report here that the activated GTP-bound form of RhoB is increased rapidly within 5 min of exposure to UVB, and then RhoB protein levels increased concomitantly with EGF receptor (EGFR) activation. Inhibition of UVB-induced EGFR activation prevents RhoB protein expression and AKT phosphorylation but not the early activation of RhoB. Blocking UVB-induced RhoB expression with specific small interfering RNAs inhibits AKT and glycogen synthase kinase-3β phosphorylation through inhibition of EGFR expression. Moreover, down-regulation of RhoB potentiates UVB-induced cell apoptosis. In contrast, RhoB overexpression protects keratinocytes against UVB-induced apoptosis. These results indicated that RhoB is regulated upon UVB exposure by a two-step process consisting of an early EGFR-independent RhoB activation followed by an EGFR-dependent induction of RhoB expression. Moreover, we have demonstrated that RhoB is essential in regulating keratinocyte cell survival after UVB exposure, suggesting its potential role in photocarcinogenesis.

Published
2005

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