38 results on '"Jouin, Mélanie"'
Search Results
2. N-3 fatty acids, neuronal activity and energy metabolism in the brain
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Harbeby Emilie, Pifferi Fabien, Jouin Mélanie, Pélerin Hélène, Tremblay Sébastien, Lecomte Roger, Cunnane Stephen C., Huertas Alain, Alessandri Jean-Marc, and Guesnet Philippe
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Ageing ,Alzheimer ,Brain ,Glucose metabolism ,Glucose transporter GLUT1 ,Docosahexaenoic acid (DHA) ,N-3 fatty acids ,Oils, fats, and waxes ,TP670-699 - Abstract
The content of docosahexaenoic acid (DHA) in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1) a lower brain glucose utilization, 2) a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3) a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.
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- 2012
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3. Conversion of n-3 polyunsaturated fatty acids (PUFAs) and incorporation of docosahexaenoic acid (DHA) in cultured neural cells
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Alessandri Jean-Marc, Langelier Bénédicte, Perruchot Marie-Hélène, Extier Audrey, Pifferi Fabien, Jouin Mélanie, Delpal Serge, Lavialle Monique, and Guesnet Philippe
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docosahexaenoic acid (DHA) ,endothelial cells ,ethanolamine phosphoglycerolipids (EPG) ,n-3 PUFA conversion ,peroxisomal enzymes ,rat brain ,SH-SY5Y neuroblastoma cells ,Oils, fats, and waxes ,TP670-699 - Abstract
Docosahexaenoic acid (DHA, 22:6n-3) in membrane phospholipids originates from dietary intake of preformed DHA and from conversion of its essential precursor α-linolenic acid (ALA, 18:3n-3). Cultured cells, especially nervous cells, are increasingly used to explore the uptake, metabolism and gene transcription effects of n-3 fatty acids, raising the question of the specific metabolic fate of different fatty acids and of the physiological relevance of their concentrations in the culture medium. This paper reports experimental data that 1) compare the dose-dependent incorporation of preformed DHA into the ethanolamine phosphoglycerolipids (EPG) of neural and cerebral endothelial cells in culture with that of the developing rat brain, 2) evaluate the pathway of DHA synthesis from ALA, eicosapentaenoic acid (EPA, 20:5n-3) or n-3 docosapentaenoic acid (DPA, 22:5n-3) in a model of neuronal cells, the SH-5YSY human neuroblastoma cells, and 3) characterize in these cells the mRNA expression profile of genes involved in the fatty acid metabolism. The incorporation of preformed DHA in EPG followed, both in vivo and in vitro, a dose-response curve from which two parameters were drawn: the DHAmax, i.e. the plateau-value of the linearized dose-response curve (expressed in weight % of total fatty acids), and the DHA50, the concentration of DHA in the diet or in the culture medium corresponding to an incorporation of DHA in EPG equal to one-half the DHAmax. The ratio of DHAmax to DHA50 reflects the propensity (so-called the ‘avidity’ for DHA) of cells or tissues to incorporate the exogenous DHA. The DHAmax and the DHAmax/DHA50 ratio values of SH-SY5Y cells and of rat brain endothelial cells in culture were compared to those of the frontal cortex and hippocampus of rats chronically deficient in n-3 fatty acids and supplemented with preformed DHA. The same DHAmax/DHA50 ratio values were found in SH-SY5Y (5.2) cells and in rat brain areas (5.1-5.7) when the DHA doses were expressed in lmol DHA/liter of culture medium and in lmol DHA/10 g diet, respectively. The SH-SY5Y cells were able to produce neoformed EPA, DPA and DHA from supplemental ALA. The incorporation of neoformed EPA and DPA in EPG followed a dose-response saturating curve, while that of DHA was bell-shaped. The different pattern of neoformed DPA and neoformed DHA suggests that the conversion pathway was limited at the terminal step of DHA synthesis. The mRNA profile showed that two enzymes of the peroxisomal b-oxidation system, the L- and D-bifunctional proteins, were expressed at lower levels than those of the endoplasmic reticulum pathway (Δ6-desaturase). These data show that incorporation of preformed DHA in cultured neuroblastoma cells match physiological values, indicating that DHA uptake, acyl-CoA activation, and phospholipid acyltransferases are active. However, the synthesis and incorporation of newly formed DHA in SH-SY5Y cells responds to a critical concentration-window of precursors which could originate from the low basal expression level of peroxisomal enzymes.
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- 2007
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4. n-3 long-chain fatty acids and regulation of glucose transport in two models of rat brain endothelial cells
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Pifferi, Fabien, Jouin, Mélanie, Alessandri, Jean-Marc, Roux, Françoise, Perrière, Nicolas, Langelier, Bénédicte, Lavialle, Monique, Cunnane, Stephen, and Guesnet, Philippe
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- 2010
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5. Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes
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Safi-Stibler, Sofiane, primary, Thévenot, Etienne A., additional, Jouneau, Luc, additional, Jouin, Mélanie, additional, Seyer, Alexandre, additional, Jammes, Hélène, additional, Rousseau-Ralliard, Delphine, additional, Baly, Christine, additional, and Gabory, Anne, additional
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- 2020
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6. (n-3) Polyunsaturated Fatty Acid Deficiency Reduces the Expression of Both Isoforms of the Brain Glucose Transporter GLUT1 in Rats
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Pifferi, Fabien, Roux, Françoise, Langelier, Bénédicte, Alessandri, Jean-Marc, Vancassel, Sylvie, Jouin, Mélanie, Lavialle, Monique, and Guesnet, Philippe
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- 2005
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7. Pre-conceptional maternal metabolic status influences hepatic metabolome in male offspring
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Ralliard-Rousseau, Delphine, Jouin, Mélanie, Jouneau, Luc, Junien, Claudine, Thevenot, Etienne, Baly, Christine, Gabory, Anne, and SAFI-STIBLER, Sofiane
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Animal biology ,DOHaD, Obésité, Perte de poids, Préconception, Métabolisme, Métabolomique, Foie, Hypothalamus, Bulbe Olfactif ,Biologie animale ,Biologie du développement ,Development Biology - Abstract
Background/Aims Maternal obesity is associated with fertility disorders, obstetric complications, and development of metabolic syndrome in offspring. The recommendation to overweight or obese women is to lose weight before pregnancy, but the impact of these prescriptions on the offspring health is insufficiently studied. Previous results on late-term mice fetuses have shown that maternal obesity leads to fetal growth restriction and to the modification of epigenetic machinery-related gene expression in fetal liver and placenta. Moreover, fetuses from the preconceptional weight loss maternal group normalize their growth, but some fetal genes stay differentially expressed. Method We analysed the metabolic phenotype of offspring born to control (CTRL), obese (OB) or weight loss after diet-induced obesity (WL) mothers. To highlight a possible conditioning effect, offspring were either fed a control (CD) or a high fat diet (HFD). Their metabolism and olfactory behavior were monitored for up to 6 months. Then, we analyzed the metabolome of three tissues involved in food intake and nutrient management (liver, olfactory bulb and hypothalamus) in male adult offspring. Results Multiple Factorial Analysis integration of offspring phenotypic data showed a major influence of the post-weaning diet and pointed a difference in HFD-fed males according to their maternal group (OB vs WL). This confirmed a sex-dependant metabolic conditioning by the maternal environment. The olfactory sensitivity, measured by electro-olfactogram, was reduced in WL male offspring, whatever the postnatal diet. The metabolomics study annotated 278, 258 and 200 metabolites in the liver, olfactory bulb and hypothalamus respectively. Again, the post-weaning diet had a major effect in the three tissues but interestingly, the maternal group also influenced the hepatic metabolome of adult offspring. Conclusions These data, integrating metabolism, olfactory behavior and metabolome, provide new and original information on the effects of preconceptional maternal metabolic status in the offspring health conditioning upon diet challenges.
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- 2019
8. Trajectoires pondérales maternelles préconceptionnelles (TPMP) et effet sur la santé de la descendance
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SAFI-STIBLER, Sofiane, Panchenko, Polina, Jouin, Mélanie, Jouneau, Luc, VOISIN, Sarah, Rousseau-Ralliard, Delphine, Jammes, Hélène, Junien, Claudine, Thevenot, Eric, Baly, Christine, Gabory, Anne, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Domaine expérimental Bourges-La Sapinière (BOURGES), Institut National de la Recherche Agronomique (INRA), Neurobiologie de l'olfaction (NBO), Université Paris Saclay (COmUE), and Adebiotech. FRA.
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[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,ComputingMilieux_MISCELLANEOUS - Abstract
National audience
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- 2018
9. Effect of Maternal Obesity and Preconceptional Weight Loss on Male and Female Offspring Metabolism and Olfactory Performance in Mice
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Panchenko, Polina E., primary, Lacroix, Marie-Christine, additional, Jouin, Mélanie, additional, Voisin, Sarah, additional, Badonnel, Karine, additional, Lemaire, Marion, additional, Meunier, Nicolas, additional, Safi-Stibler, Sofiane, additional, Persuy, Marie-Annick, additional, Jouneau, Luc, additional, Durieux, Didier, additional, Lecoutre, Simon, additional, Jammes, Hélène, additional, Rousseau-Ralliard, Delphine, additional, Breton, Christophe, additional, Junien, Claudine, additional, Baly, Christine, additional, and Gabory, Anne, additional
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- 2019
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10. Effects of preconceptional maternal weight trajectories on offspring health
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SAFI-STIBLER, Sofiane, Panchenko, Polina, Jouin, Mélanie, Jouneau, Luc, VOISIN, Sarah, Junien, Claudine, Gabory, Anne, Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Biologie du Développement et Reproduction (BDR), and École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
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maternal obesity ,obesity ,obésité ,syndrome métabolique ,epigenetics ,offspring ,metabolic x syndrome ,progéniture ,weight mass ,weight loss ,poids ,[SDV.BDD]Life Sciences [q-bio]/Development Biology - Abstract
Since the 90’s, obesity became pandemic. Nutritional environment has an important impact during development, leading to the later onset of non-communicable diseases. Maternal environment may affect offspring development through epigenetic mechanisms, regulating gene expression and microbiota, which is a major actor of metabolism. In order to reduce fertility troubles and obstetrical complications caused by obesity, it is now recommended for women who plan a pregnancy to lose weight before conception. However, the long-term effects of this preconception weight loss are not well described in the literature. We aim to identify whether maternal weight loss prior to conception can prevent the development of metabolic syndrome at the adult age. We previously highlighted in a mouse model the high sensitivity of the epigenetic machinery gene expression, and particularly histone acetylation pathway, to maternal obesity. Preconceptional weight loss appears beneficial for fetal growth, but some effects of previous obesity were retained in offspring transcriptome. During my PhD, I will precise:- the offspring phenotype using metabolomics of adult liver, olfactory bulb and hypothalamus (LC-HRMS),- the epigenomic analysis by an histone acetylation study in fetal liver (ChIP-seq,- the microbiota component with an analysis of maternal and offspring gut microbiota (16S rRNA-seq).The correlation of metabolic parameters, epigenomic state and gut microbiota will give us information about the mechanisms of maternal diet’s effects and their participation to adult health conditioning.
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- 2017
11. A primate model to study epigenetic mechanisms involved in metabolism regulation in response to nutritional stress
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Jouin, Mélanie, Tessonneau, Léanna, Terrien, Jérémy, Gabory, Anne, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université Paris Saclay (COmUE), Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Société Francophone-DOHaD. FRA., Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Mécanismes adaptatifs : des organismes aux communautés (MECADEV), and Muséum national d'Histoire naturelle (MNHN)
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mouse lemur ,animal model ,[SDV]Life Sciences [q-bio] ,epigenetic mechanisms ,régulation du metabolisme ,metabolic activity ,primate ,stress nutritionnel ,nutrition ,épigénétique ,réponse au stress ,animal modèle ,[INFO]Computer Science [cs] ,[SDV.BDD]Life Sciences [q-bio]/Development Biology - Abstract
International audience; The grey mouse lemur ( Microcebus murinus) is an arboreal primate originating from Madagascar, where it faces environmental conditions with strong contrasts between summer and winter seasons, in particular for food and water availability. Seasonal varia-tions result in adaptive response inducing energetic metabolism and behavioral changes that are fully reproducible in captivity. Characterized by its great phenotypic fiexibility, this primate appears as an interest ing mode!to evaluate the raies of epigenetic me-chanisms in modulating the adaptive responses to environmental modifications. In order to determine the impact of nutritional stress on epigenetic mechanisms, we submitted adult male mouse lemurs to either a control diet (CTL; ad libitum; N=6) or to an energetic challenge (CR; 40% calorie restriction; N=6) for 5 weeks, at the end of the winter season. Animals were then monitored for body mass, food intake, core temperature, metabolic performances and glucose tolerance. Liver biopsies were also performec\ before and after the experimental period, for both control and challenged animals. While calorie restriction had no major effect on body weight, core temperature· or metabolic performance, we observed an improvement of glucose tolerance in CR animals. We further investigated whether this result could be reflected at the epigenetic level. In a first approach, we focusecl on liver global DNA methylation. RNA and DNA were coextracted and DNA methylation measured by LUlMA (luminometric methylation as-say). Global liver DNA methylation was 65% ± 3% in Microcebus murinus. This level was not modified by the season and not affected by calorie restriction. Additional stuclies are needed to understand the molecular mechanisms that underlie the physiological changes displayed in response to environmental changes in the mouse lemur. A specific emphasis could be made on DNA methylation of gene promoters involved in lipid and glucose metabolism. This preliminary project challenges the role of epigenetic plasticity in adaptive processes and highlights the role that might play the mouse lemur as an animal model to decipher the mechanisms underlying phenotypic flexibility.
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- 2016
12. Preconceptional and gestational effects of maternal weight trajectories on olfactory performances in mice offspring
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Lacroix, Marie-Christine, VOISIN, Sarah, Meunier, Nicolas, Jouin, Mélanie, Badonnel, Karine, Panchenko, Polina, Persuy, Marie-Annick, Durieux, Didier, Gabory, Anne, Baly, Christine, Neurobiologie de l'olfaction (NBO), Institut National de la Recherche Agronomique (INRA), Université Paris Saclay (COmUE), Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université Paris-Sud - Paris 11 (UP11), and Société Francophone-DOHaD. FRA.
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[SDV]Life Sciences [q-bio] ,[INFO]Computer Science [cs] - Abstract
National audience; Preconceptional or inter-pregnancy weight loss is often recommenclecl to obese future mothers as a preventive action to protect offspring clevelopment from deleterious effects of endocrine impairments du-ring pregnancy and lactation. However, the benefits of such a maternal weight control on offspring long-term health remain poorly investigated. Olfactory sensitivity and associated behaviours are influenced by the metabolic status (1-2). Ils alteration has been described in varions diet-induced inoclels of metabolic imbalances, such as diet-induced obesity (3) and calorie restriction (4) or in bariatric surgery studies (5). As maternal environment could impact progeny health at long-term according to the known DOHaD concept, we investigated the effect of pre-gestational maternal weight control on off spring olfactory sensitivity in a mouse model recently developed (6): Mice were either fed with a control diet (CD) , a high-fat diet (HFD) or a HFD switched to a CD one 2 months before conception to induce a weight loss (WL) . After birth, pups were divided in two groups at weaning and were fed with CD or HFD for 5 months. Metabolic measures revealed clear-cut endocrine differences in offspring reflecting their diet status. Animals were tested for their olfactory-based behaviour in a buriecl cookie test and a 2-hole board olfactory preference test. The post-weaning diet predominantly influenced pu p's olfactory sensitivity and preferences as compared to the maternal one. Interestingly, maternal weight loss didn't prevent the development of olfactory impairments observed as early as after 3 weeks uncler a HFD, i.e. much before the appearance of endocrine alterations in the offspring. Surprisingly, we observed that peripheral olfactory mucosa neuronal response was clearly diminished in the electro-olfactograms recorded after 5 months of diet in offspring barn from WL mothers regardless the postweaning diet, compared to those born from CD and HFD mothers. We conclude that post-weaning cliet recommendations are essential to optimize the preventive effect of a pre-gestational or gestational weight loss on the development of olfactory impairments that could participate to food intake deregulation. If the maternal preconceptional weight loss only partially counteracts post-weaning diet consequences, its intergenerational eff'ect on peripheral olfactory sensi-tivity should be further investigated at molecular level.
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- 2016
13. Mémoire épigénétique des trajectoires pondérales maternelles préconceptionnelles au cours du développement chez la souris
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Panchenko, Polina, Voisin, Sarah, Jouin, Mélanie, Jouneau, Luc, Prézelin, Audrey, Jammes, Hélène, Junien, Claudine, Gabory, Anne, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), and Institut National de Recherche Agronomique (INRA). UAR Département Physiologie Animale et Systèmes d'Elevage (0558).
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mémoire épigénétique ,phénotype ,obésité préconceptionnelle ,dohad ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD]Life Sciences [q-bio]/Development Biology - Abstract
National audience; Selon le concept des origines développementales de la santé et des maladies, l'obésité maternelle prédispose la descendance à développer le syndrome métabolique à l'âge adulte. Une perte de poids préconceptionnelle est actuellement recommandée aux femmes obèses, mais ses effets pour la croissance du fœtus et pour la santé à l'âge adulte sont encore mal décrits. L'histoire pondérale maternelle pourrait être "mémorisée" par des mécanismes épigénétiques, perturbant l'expression de gènes clés du développement et du métabolisme et conditionnant ainsi à une susceptibilité accrue aux pathologies métaboliques. Nos travaux ont pour objectifs 1) d'étudier les effets de l'obésité maternelle sur le développement fœto-placentaire ainsi que les mécanismes épigénétiques sous-jacent 2) d'évaluer si la perte de poids préconceptionnelle entraine un bénéfice quant à ces effets ou si une mémoire de l'histoire pondérale maternelle est conservée dans la descendance. Nous avons développé un nouveau modèle murin : en période préconceptionnelle, des femelles ont été nourries pendant 4 mois avec un régime riche en lipides (HFD, pour high fat diet), entrainant une obésité (groupe OB), ou avec un régime contrôle (CD, pour control diet; groupe CTRL). Un troisième groupe a été nourri 2 mois avec le régime HFD puis 2 mois avec le régime CD, induisant une perte de poids (groupe WL pour weight loss). Nous avons le phénotype fœtal et placentaire au terme de la gestation et l'expression des gènes codants pour des modificateurs épigénétiques et des gènes impliqués dans le développement et le métabolisme, dans le foie fœtal, le labyrinthe et la zone jonctionnelle placentaires. Les fœtus OB présentent une restriction de croissance fœtale : ils sont "petits pour l'âge gestationnel" à terme. Ce phénotype est associé à une réponse transcriptionnelle dans le foie fœtal et le labyrinthe placentaire. Les gènes de la machinerie enzymatique impliquée dans l’acétylation des histones sont particulièrement affectés par l’obésité maternelle. La perte de poids a permis d’améliorer la croissance fœtale et l’expression génique, sans toutefois assurer une correction complète des effets de l’obésité préconceptionnelle. La machinerie épigénétique, en lien avec la restriction de croissance fœtale, semble donc particulièrement sensible au métabolisme maternel. Notre étude souligne l’importance de comprendre le rôle des régulateurs épigénétiques dans le contexte des pathologies métaboliques. Peu de preuves dans la littérature attestent les effets de l'intervention nutritionnelle chez les sujets obèses, chez l'homme et chez les rongeurs. Notre modèle nous permet d'apporter les premiers éléments sur les mécanismes du conditionnement développemental par la perte de poids préconceptionnelle maternelle.
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- 2016
14. Additional file 3: of Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice
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Panchenko, Polina, Voisin, Sarah, Jouin, Mélanie, Jouneau, Luc, Prézelin, Audrey, Lecoutre, Simon, Breton, Christophe, Jammes, Hélène, Junien, Claudine, and Gabory, Anne
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GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) - Abstract
Description of the selection criteria of genes for the custom TLDA design and related bibliographic references.
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- 2016
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15. Additional file 1: of Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice
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Panchenko, Polina, Voisin, Sarah, Jouin, Mélanie, Jouneau, Luc, Prézelin, Audrey, Lecoutre, Simon, Breton, Christophe, Jammes, Hélène, Junien, Claudine, and Gabory, Anne
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Supplementary Figures S1 to S6. Food intake (FI) to body weight (BW) ratio in females during the preconceptional period. (a) P
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- 2016
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16. Striking sexual dimorphism in nutritional programming of health and diseases: the epigenetic basis
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Gabory, Anne, Wu, Qihan, Ferry, Laure, Panchenko, Polina, Jouin, Mélanie, Attig, Linda, Junien, Claudine, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and University of Cape Town (UCT). ZAF.
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dohad ,sexual dimorphism ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,mouse - Abstract
International audience; Research question Non-genetic heritability of susceptibility to chronic diseases is often different between male and female. The environmental factors to which an individual is exposed can leave an epigenetic footprint that dictates the coordinate expression of genes. A crucial period is the early development, when the epigenome is reprogrammed and therefore particularly sensitive to the environment. The sexual dimorphism results from the chromosomal sex (XX/XY) before gonad differentiation and a later-on complex mix of hormones and X/Y-linked genes regulating autosomal genes. The early exposure interacts with this subtle superposition, leading to specific reactions, adaptation and outcomes for men and women. Methods With several mouse model of maternal high-fat diet exposure, we demonstrate a striking sexual dimorphism of programming trajectories in different tissues (particularly placenta and liver) in response to the same environmental challenge. Results and Conclusion Our findings provide proof-of-concept that the epigenetic marks and modifiers may be part of the sex-specific causal variables. Their study represents a novel approach to identify sex-specific mechanisms in the origins of health and disease. The discovery of such factors should help physicians and patients anticipate disease susceptibility and may help the development of different preventative and treatment strategies precisely adapted to males and females.
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- 2015
17. Maternal obesity and weight loss: foeto-placental epigenetic programming and impact on adult offspring
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Panchenko, Polina, Jouin, Mélanie, Jouneau, Luc, Voisin, Sarah, Lemaire, Marion, Prézelin, Audrey, Catonne, Amandine, Junien, Claudine, Gabory, Anne, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Abcam. GBR., and École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
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[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2015
18. The epigenetic basis of sexual dimorphism in nutritional programming of health and diseases
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Gabory, Anne, Wu, Qihan, Panchenko, Polina, Voisin, Sarah, Jouin, Mélanie, Attig, Linda, Junien, Claudine, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Abcam. GBR.
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[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD]Life Sciences [q-bio]/Development Biology - Abstract
International audience; Research question: The non-genetic heritability of susceptibility to chronic diseases is often different between males and females. The environment factors can leave epigenetic footprints on the DNA that dictate a coordinated expression of genes. A crucial period is the early development, when the epigenome is being reprogrammed and therefore particularly sensitive to the environment. Sexual dimorphism stems from the chromosomal sex (XX/XY) before gonad differentiation and from a later-on complex mix of hormones and X/Y-linked genes regulating autosomal genes. Early exposure interacts with these hormonal and genetic factors, leading to specific reactions, adaptations and outcomes for men and women. Methods: With several mouse models of maternal high-fat diet exposure, we demonstrate a striking sexual dimorphism of programming trajectories in different tissues, particularly placenta and liver, in response to the same environmental challenge. Results and Conclusion: Our findings provide proof-of-concept that epigenetic marks and modifiers may be part of the variables that causes sex-specific. This represents a novel approach to identify sex-specific mechanisms in the origins of health and disease. The discovery of such factors should help physicians and patients anticipate disease susceptibility and may help the development of prevention and treatment strategies precisely adapted to males and females.
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- 2015
19. Obésité et perte de poids maternelles : programmation épigénétique dans le placenta et effets sur le phénotype des descendants adultes
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Panchenko, Polina, Jouin, Mélanie, Jouneau, Luc, Lemaire, Marion, Prézelin, Audrey, Catonne, Amandine, Junien, Claudine, Gabory, Anne, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Hôpitaux Universitaires de Genève (HUG). CHE.
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obésité ,épigénétique ,placenta ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2015
20. Maternal preconceptional weight loss: impact on fetoplacental development and on epigenetic machinery genes expression
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Panchenko, Polina, Jouneau, Luc, Jouin, Mélanie, Lemaire, Marion, Junien, Claudine, Gabory, Anne, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Latin American Society for Maternal Fetal Interaction and Placenta (SLIMP). ARG., and École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
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obesity ,fetal programming ,nutrition ,gestation ,placenta ,dohad ,sex ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,maternal environment ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2015
21. Effects of maternal preconception weight trajectory on offspring health
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Lemaire, Marion, Jouin, Mélanie, Panchenko, Polina, Baklanov, Alexandr, Junien, Claudine, Gabory, Anne, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Société Francophone pour la Recherche et l'Education sur les Origines Développementales, Environnementales et Epigénétiques de la Santé et des Maladies (SF-DOHAD). FRA.
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maternal obesity ,preconception weight loss ,nutrition ,sexual dimorphism ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,developmental origin of health and disease - Abstract
National audience; An increasing number of childbearing age women are overweight or obese. Current recommendations include a preconceptional weight loss (WL) of 5 to 10% to reach a normal pre-pregnancy body mass index. Although there is evidence that preconceptional WL reduces pregnancy complications but can induce growth retardation or preterm delivery , the long-term consequences on offspring health remain unknown. ln the light of the Developmental Origins of Health and Disease (DOHaD) hypothesis, maternal pre-pregnancy weight trajectories could have beneficial, neutral or detrimental long-term effects on offspring• Our aim was to investigate the outcomes of preconception WL in obese C57BL/6J female mice on offspring susceptibility to an obesogenic diet in later life. Female mice of the WL group were led a High-Fat Diet (HFD) for two months and a control diet (CD) for the following two months. Two control groups consisted in: Lean and Obese Control (LC and OC), receiving either the CD or HFD diet for four months and during gestation/lactation. At weaning, offspring were led either a HFD or a CD. Weight, calorie intake, glucose metabolism and body composition were followed until sacrifice at 6 months. No significant differences were observed preweaning between LC and WL offspring for weight and glycaemia. As for OC offspring, they had a higher body weight and lasting hyperglycemia. Sexual dimorphism was observed alter weaning for all parameters studied and as adults, all HFD-fed offspring had an increased body weight, adiposity and lasting hyperglycemia, independently of maternal group. ln our model, the offspring phenotype relies mainly on the postweaning diet. Despite abundant literature on in utero exposure to a one paper reported the absence of association between offspring parameters and preconception HFD. More investigations are needed to complete this phenotyping and at epigenetic levels to draw conclusions about maternal preconception trajectory effects on offspring health.
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- 2014
22. A mice model of preconceptional maternal weight loss
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Jouin, Mélanie, Panchenko, Polina, Lemaire, Marion, Gabory, Anne, Junien, Claudine, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Société Francophone pour la Recherche et l'Education sur les Origines Développementales, Environnementales et Epigénétiques de la Santé et des Maladies (SF-DOHAD). FRA.
- Subjects
preconception weight loss ,nutrition ,sexual dimorphism ,mouse model ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,developmental origin of health and disease - Abstract
National audience; More and more women of childbearing age are overweight or obese. To reduce infertility and Obstetric complications, weight loss is recommended. However, whether this weight loss has positive or deleterious consequences on fetal growth and the long-term health of the children remains to be clarified. Our aim was to develop a mice model of preconceptional maternal weight loss (WL) for further studies within the framework of the DOHaD field, with relevance to human. C57BL/6J female mice received a high-fat diet (HFD) for two months, then a control diet (CD) for Two months. Body weight and food intake were recorded twice a week. At 2 and 4 months, lasting glycemia, insulin and cholesterol were measured and glucose metabolism determined with oral glucose tolerance test (OGTT). Mice were mated with males under a CD and their weight gain was followed during gestation. Control mothers received a CD (lean control) or HFD (obese control) during preconceptionallgestation/lactation period. Alter offspring weaning, maternal adipose tissues, liver, kidneys and heart were weighed to evaluate maternal body composition and adiposity. Alter 2 months on a HFD, females showed a significant weight gain compared to CD-led mice, were hyperglycemic, glucose intolerant and hypercholesterolemic. Alter two months on a CD, normalization of weight, carbohydrate and lipid metabolism was observed. At the end of lactation, WL females body composition was not distinguishable from lean control. A switch from HFD to a CD induce a massive WL with normalisation of metabolic state and body composition in obese females. This model is therefore suitable to investigate effects of maternal ponderal trajectories or massive preconceptional loss such as that induced by bariactric surgery in human obese patients on offspring development and their long-term health and the underlying molecular mechanisms.
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- 2014
23. Impact on epigenetic machinery genes expression and on foeto-placental development of preconceptional maternal weight loss
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Panchenko, Polina, Jouneau, Luc, Jouin, Mélanie, Lemaire, Marion, Junien, Claudine, Gabory, Anne, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Société Francophone pour la Recherche et l'Education sur les Origines Développementales, Environnementales et Epigénétiques de la Santé et des Maladies (SF-DOHAD). FRA.
- Subjects
intrauterine growth restriction ,placenta ,IUGR ,embryonic structures ,high fat diet ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,epigenetic ,preconceptional weight loss - Abstract
National audience; Whether the currently recommended preconceptional weight loss (WL) for obese women is beneficial/detrimental for fetoplacental development remains poorly explored and even less on the long term. Obesity, even if corrected before conception, and the WL processes could be "memorized" via epigenetic mechanisms perturbing expression of key developmental genes leading to altered fetal programming. Our aim was to investigate the effects of maternal WL alter diet-induced obesity on fetoplacental development and on gene expression in male and female mice offspring. During the preconception period, female C57BI/6J mice were led a high-fat diet (HFD) for two months, leading to obesity and then a control die! (CD) for two months, leading to a complete WL. ln parallel, obese control group (OC) was led a HFD and lean control group (LC) a CD throughout the preconceptional period and gestation. At embryonic day 18 (E18.5), OC fetuses presented intrauterine growth retardation (IUGR), while WL fetuses, despite maternal weight normalization before conception, showed a significantly decreased weight at term which was intermediate between OC and LC fetuses. Placental weight was not affected by diet. Gene expression of 60 epigenetic machinery and 30 key developmental genes was analysed in the placental labyrinth and fetal liver using RTq-PCR Taqman custom array card. Expression of several epigenetic machinery genes was altered in OC fetuses. ln WL fetuses the level of expression of some genes was restored to the level of LC fetuses while ether genes showed similar profiles as in OC fetuses. Thus correction of maternal obesity by nutritional intervention in the preconceptional period only partially protects the offspring from IUGR. We show that modulation of the histone acetylation-deacetylation switch could play a role in fetal programming. Further studies at the genome-wide level will elucidate the epigenetic targets and mechanisms of placental/fetal programming triggered by maternal ponderal trajectories.
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- 2014
24. Mécanismes épigénétiques des effets du métabolisme maternel sur le développement de la descendance mâle et femelle
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Gabory, Anne, Jouin, Mélanie, Panchenko, Polina E., and Safi-Stibler, Sofiane
- Abstract
Les expositions précoces à des facteurs de stress biologiques, chimiques ou sociaux peuvent avoir des répercussions à long terme sur la santé des adultes. Les processus qui sous-tendent ces origines développementales de la santé et des maladies ne sont pas entièrement compris. Les mécanismes épigénétiques, qui gouvernent la détermination de l’identité cellulaire au cours de la différenciation des organes, sont d’excellents candidats pour expliquer comment des évènements précoces peuvent modifier la physiologie de l’adulte.Les descendants mâles nés de mères souris obèses ont un risque plus élevé d’avoir un petit poids de naissance et de devenir obèses à l’âge adulte. L’expression des gènes codants les modificateurs épigénétiques est altérée dans le placenta et le foie fœtal. Les descendants de mères ayant perdu du poids avant la gestation, grâce à une intervention nutritionnelle, ne présentent pas d’anomalie phénotypique, mais l’expression des gènes n’est pas normalisée. Des phénotypes délétères pourraient alors apparaître avec le vieillissement.
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- 2024
- Full Text
- View/download PDF
25. Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice
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Panchenko, Polina E., primary, Voisin, Sarah, additional, Jouin, Mélanie, additional, Jouneau, Luc, additional, Prézelin, Audrey, additional, Lecoutre, Simon, additional, Breton, Christophe, additional, Jammes, Hélène, additional, Junien, Claudine, additional, and Gabory, Anne, additional
- Published
- 2016
- Full Text
- View/download PDF
26. Maternal preconceptional weight loss: Impact on feto-placental development and on epigenetic machinery genes expression
- Author
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Panchenko, Polina, primary, Jouneau, Luc, additional, Jouin, Mélanie, additional, Lemaire, Marion, additional, Junien, Claudine, additional, and Gabory, Anne, additional
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- 2015
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27. Epigénétique et Nutrition : impacts de l’alimentation maternelle sur le développement placentaire et la santé de la descendance
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Panchenko, Polina E., primary, Lemaire, Marion, additional, Fneich, Sara, additional, Voisin, Sarah, additional, Jouin, Mélanie, additional, Junien, Claudine, additional, and Gabory, Anne, additional
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- 2015
- Full Text
- View/download PDF
28. Gene expression of fatty acid transport and binding proteins in the blood–brain barrier and the cerebral cortex of the rat: Differences across development and with different DHA brain status
- Author
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Pélerin, Hélène, primary, Jouin, Mélanie, additional, Lallemand, Marie-Sylvie, additional, Alessandri, Jean-Marc, additional, Cunnane, Stephen C., additional, Langelier, Bénédicte, additional, and Guesnet, Philippe, additional
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- 2014
- Full Text
- View/download PDF
29. Omega 3 fatty acids and energy supply: impact on glucose transport
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Pifferi, Fabien, Roux, Françoise, Langelier, Benedicte, Alessandri, Jean Marc, Vancassel, Sylvie, Jouin, Mélanie, Lavialle, Monique, Guesnet, Philippe, Laboratoire de nutrition et sécurité alimentaire, Institut National de la Recherche Agronomique (INRA), Mécanismes d'action des toxiques sur les membranes du système nerveux, and Institut National de la Santé et de la Recherche Médicale (INSERM)
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[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,ComputingMilieux_MISCELLANEOUS - Abstract
National audience
- Published
- 2005
30. Sex-specific epigenetic impact of preconceptional maternal weight loss on foeto-placental development
- Author
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Panchenko, Polina, primary, Jouin, Mélanie, additional, Jouneau, Luc, additional, Lemaire, Marion, additional, Junien, Claudine, additional, and Gabory, Anne, additional
- Published
- 2014
- Full Text
- View/download PDF
31. n-3 PUFA status affects expression of genes involved in neuroenergetics differently in the fronto-parietal cortex compared to the CA1 area of the hippocampus: Effect of rest and neuronal activation in the rat
- Author
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Harbeby, Emilie, primary, Jouin, Mélanie, additional, Alessandri, Jean-Marc, additional, Lallemand, Marie-Sylvie, additional, Linard, Alain, additional, Lavialle, Monique, additional, Huertas, Alain, additional, Cunnane, Stephen C., additional, and Guesnet, Philippe, additional
- Published
- 2012
- Full Text
- View/download PDF
32. Omega-3 Fatty Acids from Fish Oil Lower Anxiety, Improve Cognitive Functions and Reduce Spontaneous Locomotor Activity in a Non-Human Primate
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Vinot, Nina, primary, Jouin, Mélanie, additional, Lhomme-Duchadeuil, Adrien, additional, Guesnet, Philippe, additional, Alessandri, Jean-Marc, additional, Aujard, Fabienne, additional, and Pifferi, Fabien, additional
- Published
- 2011
- Full Text
- View/download PDF
33. A Human-Mouse Chimera of the α3α4α5(IV) Collagen Protomer Rescues the Renal Phenotype in Col4a3−/− Alport Mice
- Author
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Heidet, Laurence, primary, Borza, Dorin-Bogdan, additional, Jouin, Mélanie, additional, Sich, Mireille, additional, Mattei, Marie-Geneviève, additional, Sado, Yoshikazu, additional, Hudson, Billy G., additional, Hastie, Nicholas, additional, Antignac, Corinne, additional, and Gubler, Marie-Claire, additional
- Published
- 2003
- Full Text
- View/download PDF
34. N-3 fatty acids, neuronal activity and energy metabolism in the brain
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Harbeby, Emilie, Pifferi, Fabien, Jouin, Mélanie, Pélerin, Hélène, Tremblay, Sébastien, Lecomte, Roger, Cunnane, Stephen C., Huertas, Alain, Alessandri, Jean-Marc, Guesnet, Philippe, Harbeby, Emilie, Pifferi, Fabien, Jouin, Mélanie, Pélerin, Hélène, Tremblay, Sébastien, Lecomte, Roger, Cunnane, Stephen C., Huertas, Alain, Alessandri, Jean-Marc, and Guesnet, Philippe
- Abstract
The content of docosahexaenoic acid (DHA) in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1) a lower brain glucose utilization, 2) a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3) a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.
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- 2012
- Full Text
- View/download PDF
35. Conversion of n-3 polyunsaturated fatty acids (PUFAs) and incorporation of docosahexaenoic acid (DHA) in cultured neural cells
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Alessandri, Jean-Marc, Langelier, Bénédicte, Perruchot, Marie-Hélène, Extier, Audrey, Pifferi, Fabien, Jouin, Mélanie, Delpal, Serge, Lavialle, Monique, Guesnet, Philippe, Alessandri, Jean-Marc, Langelier, Bénédicte, Perruchot, Marie-Hélène, Extier, Audrey, Pifferi, Fabien, Jouin, Mélanie, Delpal, Serge, Lavialle, Monique, and Guesnet, Philippe
- Abstract
Docosahexaenoic acid (DHA, 22:6n-3) in membrane phospholipids originates from dietary intake of preformed DHA and from conversion of its essential precursor α-linolenic acid (ALA, 18:3n-3). Cultured cells, especially nervous cells, are increasingly used to explore the uptake, metabolism and gene transcription effects of n-3 fatty acids, raising the question of the specific metabolic fate of different fatty acids and of the physiological relevance of their concentrations in the culture medium. This paper reports experimental data that 1) compare the dose-dependent incorporation of preformed DHA into the ethanolamine phosphoglycerolipids (EPG) of neural and cerebral endothelial cells in culture with that of the developing rat brain, 2) evaluate the pathway of DHA synthesis from ALA, eicosapentaenoic acid (EPA, 20:5n-3) or n-3 docosapentaenoic acid (DPA, 22:5n-3) in a model of neuronal cells, the SH-5YSY human neuroblastoma cells, and 3) characterize in these cells the mRNA expression profile of genes involved in the fatty acid metabolism. The incorporation of preformed DHA in EPG followed, both in vivo and in vitro, a dose-response curve from which two parameters were drawn: the DHAmax, i.e. the plateau-value of the linearized dose-response curve (expressed in weight % of total fatty acids), and the DHA50, the concentration of DHA in the diet or in the culture medium corresponding to an incorporation of DHA in EPG equal to one-half the DHAmax. The ratio of DHAmax to DHA50 reflects the propensity (so-called the ‘avidity’ for DHA) of cells or tissues to incorporate the exogenous DHA. The DHAmax and the DHAmax/DHA50 ratio values of SH-SY5Y cells and of rat brain endothelial cells in culture were compared to those of the frontal cortex and hippocampus of rats chronically deficient in n-3 fatty acids and supplemented with preformed DHA. The same DHAmax/DHA50 ratio values were found in SH-SY5Y (5.2) cells and in rat brain areas (5.1-5.7) when the DHA doses were expressed in lmol DHA/liter of culture medium and in lmol DHA/10 g diet, respectively. The SH-SY5Y cells were able to produce neoformed EPA, DPA and DHA from supplemental ALA. The incorporation of neoformed EPA and DPA in EPG followed a dose-response saturating curve, while that of DHA was bell-shaped. The different pattern of neoformed DPA and neoformed DHA suggests that the conversion pathway was limited at the terminal step of DHA synthesis. The mRNA profile showed that two enzymes of the peroxisomal b-oxidation system, the L- and D-bifunctional proteins, were expressed at lower levels than those of the endoplasmic reticulum pathway (Δ6-desaturase). These data show that incorporation of preformed DHA in cultured neuroblastoma cells match physiological values, indicating that DHA uptake, acyl-CoA activation, and phospholipid acyltransferases are active. However, the synthesis and incorporation of newly formed DHA in SH-SY5Y cells responds to a critical concentration-window of precursors which could originate from the low basal expression level of peroxisomal enzymes.
- Published
- 2007
- Full Text
- View/download PDF
36. A Human-Mouse Chimera of the α3α4α5(IV) Collagen Protomer Rescues the Renal Phenotype in Col4a3−/−Alport Mice
- Author
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Heidet, Laurence, Borza, Dorin-Bogdan, Jouin, Mélanie, Sich, Mireille, Mattei, Marie-Geneviève, Sado, Yoshikazu, Hudson, Billy G., Hastie, Nicholas, Antignac, Corinne, and Gubler, Marie-Claire
- Abstract
Collagen IV is a major structural component of basement membranes. In the glomerular basement membrane (GBM) of the kidney, the α3, α4, and α5(IV) collagen chains form a distinct network that is essential for the long-term stability of the glomerular filtration barrier, and is absent in most patients affected with Alport syndrome, a progressive inherited nephropathy associated with mutation in COL4A3, COL4A4, or COL4A5 genes. To investigate, in vivo, the regulation of the expression, assembly, and function of the α3α4α5(IV) protomer, we have generated a yeast artificial chromosome transgenic line of mice carrying the human COL4A3-COL4A4locus. Transgenic mice expressed the human α3 and α4(IV) chains in a tissue-specific manner. In the kidney, when expressed onto a Col4a3−/−background, the human α3(IV) chain restored the expression of and co-assembled with the mouse α4 and α5(IV) chains specifically at sites where the human α3(IV) was expressed, demonstrating that the expression of all three chains is required for network assembly. The co-assembly of the human and mouse chains into a hybrid network in the GBM restores a functional GBM and rescues the Alport phenotype, providing further evidence that defective assembly of the α3-α4-α5(IV) protomer, caused by mutations in any of the three chains, is the pathogenic mechanism responsible for the disease. This line of mice, humanized for the α3(IV) collagen chain, will also provide a valuable model for studying the pathogenesis of Goodpasture syndrome, an autoimmune disease caused by antibodies against this chain.
- Published
- 2003
- Full Text
- View/download PDF
37. [Epigenetics and Nutrition: maternal nutrition impacts on placental development and health of offspring].
- Author
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Panchenko PE, Lemaire M, Fneich S, Voisin S, Jouin M, Junien C, and Gabory A
- Subjects
- Adult, Animals, Cardiovascular Diseases embryology, Cardiovascular Diseases physiopathology, DNA Methylation, Diet, High-Fat adverse effects, Disease Susceptibility, Female, Fetal Nutrition Disorders etiology, Fetal Nutrition Disorders prevention & control, Histones metabolism, Humans, Infant, Newborn, Male, Malnutrition physiopathology, Metabolic Syndrome embryology, Metabolic Syndrome physiopathology, Mice, Models, Biological, Obesity embryology, Obesity physiopathology, Placenta physiopathology, Pregnancy, Pregnancy Complications physiopathology, Prenatal Exposure Delayed Effects, Prenatal Nutritional Physiological Phenomena, Protein Processing, Post-Translational, Rabbits, Sex Characteristics, Embryonic Development genetics, Epigenesis, Genetic, Maternal Nutritional Physiological Phenomena, Placenta physiology
- Abstract
The environment, defined broadly by all that is external to the individual, conditions the phenotype during development, particularly the susceptibility to develop non-communicable diseases. This notion, called Developmental Origins of Health and Disease (DOHaD), is based on numerous epidemiological studies as well as animal models. Thus, parental nutrition and obesity can predispose the offspring to develop metabolic and cardiovascular diseases in adulthood. The known underlying mechanisms include an altered development of tissues that adapt to maternal metabolic condition, and a placental dysfunction, which in turn impacts fetal growth and development. Epigenetic mechanisms modulate gene expression without affecting the DNA sequence itself. The main epigenetic marks are DNA methylation and histone post-translational modifications. These marks are erased and set-up during gametogenesis and development in order to ensure cellular identity. Therefore, they can lead to a memorisation of early environment and induce long-term alteration of cell and tissue functions, which will condition the susceptibility to non-communicable diseases. The placenta is a programming agent of adult disease. The environment, such as smoking or psychosocial stress, is able to modify epigenetic processes in placenta, such as small RNA expression and DNA methylation. We showed that placenta is sensitive to maternal obesity and maternal nutrition, in terms of histology, transcription and epigenetic marks. A clear sexual dimorphism is remarkable in the placental response to maternal environment. In adulthood, the phenotype is also different between males and females. Epigenetic mechanisms could underlie this differential response of males and females to the same environment. The DOHaD can no longer be ignored in Biology of Reproduction. The prevention of non-communicable diseases must take this new paradigm into account. Research will allow a better comprehension of the mechanisms of this early conditioning and the marked sexual dimorphism it is associated to., (© Société de Biologie, 2015.)
- Published
- 2015
- Full Text
- View/download PDF
38. A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice.
- Author
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Heidet L, Borza DB, Jouin M, Sich M, Mattei MG, Sado Y, Hudson BG, Hastie N, Antignac C, and Gubler MC
- Subjects
- Animals, Autoantibodies metabolism, Autoantigens immunology, Basement Membrane metabolism, Collagen Type IV immunology, Collagen Type IV metabolism, Extracellular Matrix Proteins metabolism, Humans, Kidney metabolism, Kidney pathology, Mice, Mice, Knockout, Mice, Transgenic, Nephritis, Hereditary metabolism, Nephritis, Hereditary pathology, Phenotype, Protein Isoforms metabolism, Protein Subunits genetics, RNA, Messenger metabolism, Autoantigens genetics, Chimera, Collagen Type IV genetics, Kidney physiopathology, Nephritis, Hereditary genetics
- Abstract
Collagen IV is a major structural component of basement membranes. In the glomerular basement membrane (GBM) of the kidney, the alpha3, alpha4, and alpha5(IV) collagen chains form a distinct network that is essential for the long-term stability of the glomerular filtration barrier, and is absent in most patients affected with Alport syndrome, a progressive inherited nephropathy associated with mutation in COL4A3, COL4A4, or COL4A5 genes. To investigate, in vivo, the regulation of the expression, assembly, and function of the alpha3alpha4alpha5(IV) protomer, we have generated a yeast artificial chromosome transgenic line of mice carrying the human COL4A3-COL4A4 locus. Transgenic mice expressed the human alpha3 and alpha4(IV) chains in a tissue-specific manner. In the kidney, when expressed onto a Col4a3(-/-) background, the human alpha3(IV) chain restored the expression of and co-assembled with the mouse alpha4 and alpha5(IV) chains specifically at sites where the human alpha3(IV) was expressed, demonstrating that the expression of all three chains is required for network assembly. The co-assembly of the human and mouse chains into a hybrid network in the GBM restores a functional GBM and rescues the Alport phenotype, providing further evidence that defective assembly of the alpha3-alpha4-alpha5(IV) protomer, caused by mutations in any of the three chains, is the pathogenic mechanism responsible for the disease. This line of mice, humanized for the alpha3(IV) collagen chain, will also provide a valuable model for studying the pathogenesis of Goodpasture syndrome, an autoimmune disease caused by antibodies against this chain.
- Published
- 2003
- Full Text
- View/download PDF
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