Дисертації з теми "Troubles du métabolisme des lipides"
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Hilaire, Nathalie. "Métabolisme cellulaire des lipides neutres cytoplasmiques et myopathie à surcharge lipidique multisystémique." Toulouse 3, 1994. http://www.theses.fr/1994TOU30051.
Tremblay, André. "Étude du métabolisme des lipoprotéines dans diverses dyslipidémies." Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23810/23810.pdf.
Gilleron, Martine. "Structure et propriétés immunologiques de nouveaux glycolipides isolés de Mycobacterium kansasii et Mycobacterium gastri." Toulouse 3, 1991. http://www.theses.fr/1991TOU30221.
Chardigny, Jean-Michel. "Contribution à l'étude de l'influence, chez le rat, de la nature des lipides du régime alimentaire sur la composition biochimique du myocarde et sur les paramètres mécaniques et électriques du cœur isolé et perfusé par voie atriale gauche." Dijon, 1989. http://www.theses.fr/1989DIJOS011.
Forcheron, Fabien. "Métabolisme du cholestérol chez l'homme : effet du fénofibrate et expression des gènes régulateurs dans la plaque d'athérome." Lyon 1, 2005. http://www.theses.fr/2005LYO10084.
Paule, Philippe. "Modifications du profil lipidique dans les états fébriles et notamment infectieux." Bordeaux 2, 1993. http://www.theses.fr/1993BOR2M141.
Favé, Gaëlle. "Stratégies d'amélioration de la biodisponibilité des acides gras : approches physico-chimiques et enzymatiques." Aix-Marseille 2, 2006. https://tel.archives-ouvertes.fr/tel-00689483.
Bertrand, Catherine. "Purification de flavoprotéines d'origine mitochondriale et diagnostic des déficits héréditaires de l'oxydation mitochondriale des acides gras." Lyon 1, 1993. http://www.theses.fr/1993LYO1T013.
Griolet, Céline. "Troubles lipidiques chez l'insuffisant renal chronique : caractéristiques métaboliques et correction thérapeutique." Bordeaux 2, 1994. http://www.theses.fr/1994BOR2P016.
Desroches, Sophie. "Approches nutritionnelles pour le traitement du syndrome métabolique et de ses complications." Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24782/24782.pdf.
Do, Thi Nam Phuong. "Etude de polymorphisme génétique dans la dyslipidémie des patients coronariens : approches chez des patients français et vietnamiens." Bordeaux 2, 2008. http://www.theses.fr/2008BOR21599.
Elferchichi-Ben, Rhouma Miryam. "Effet du champ magnétique statique sur le métabolisme du rat." Montpellier 1, 2009. http://www.theses.fr/2009MON1T002.
Gary-Bobo, Magali. "Implication de l'adiponectine dans l'activité anti-obésité et anti-syndrome métabolique de l'antagoniste des récepteurs CB1 : effets périphériques et métaboliques du SR141716." Montpellier 1, 2006. http://www.theses.fr/2006MON13501.
Vidal, Elisa. "Caractérisation et prévention des conséquences d'un syndrome métabolique dans la rétine." Thesis, Bourgogne Franche-Comté, 2018. http://www.theses.fr/2018UBFCI006/document.
Metabolic syndrome (MetS) results from carbohydrate and lipid disorders that originate from misbalanced energy metabolism. MetS is a risk factor for type 2 diabetes that, in pathophysiological conditions, is characterized by vascular alterations, particularly in the retina, creating the diabetic retinopathy (DR). Despite it presents a barrier limiting the input of blood factors, the retina is under metabolic variations. The consequences of MetS in the retina have not been characterized. MetS would be responsible for the inflammation and microvascular alterations in the retina and could participate to the development of age-related macular degeneration (AMD). A diet rich in omega-3 long chain polyunsaturated fatty acids (LC-PUFA) i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and low omega-6 fatty acid, should participate to the prevention of insulin resistance, a feature of MetS. Such diet would be protective against AMD, the leading cause of visual impairment after the age of 55 years in Western populations. Meanwhile, the bioavailability of omega-3 in the retina, is a parameter to consider to fully take advantages of their protective effects. Yet, data on the bioavailability of fatty acids from different origins are sparse and need to be studied.Our first goal was to associate metabolic and retinal disturbances in the context of MetS. For that purpose, we evaluated the impact of a pro diabetic diet on carbohydrate and lipid metabolism in the rat, and further analyzed the function and structure of the retina. Our second objective was to compare the efficacy of phospholipids and triglycerides to improve the incorporation of omega-3 LC-PUFA in the retina and others tissues in the rat.Brown Norway (BN) rats were fed with a 60% fructose and 10% saturated lipid diet (HFHF). The results revealed fasted hyperglycaemia, glucose intolerance and insulin resistance at 8 days and afterwards, without dyslipidaemia. Thus, considering the resistance of BN rats to develop dyslipidaemia, we performed a comparative study with BN and W rats by feeding them with HFHF. Our results showed that W rats were more sensitive to lipid deregulations. However, they did not develop insulin resistance, and developed hyperglycaemia later than BN. Regarding these data, functional analyses of retina by electroretinography was performed in BN. Electroretinograms revealed a loss of cone photoreceptor sensitivity after 4 weeks of HFHF diet without other functional dysfunction.In one independent group of BN rats, choroidal neovascularization was induced by rupture of Bruch’s membrane with impact lasers in eye fundus. Retinal angiography revealed that feeding HFHF diet during 4 weeks favoured neovascular development in the retina, and activated Müller cells. Then, we wanted to compare omega-3 LC-PUFA integration in the retina by feeding Wistar rats with 6 different lipid sources. The strength of this work was to use either phospholipids, triglycerides or a mix of both, that contained either EPA or DHA as the prominent omega-3 fatty acid. Our qualitative data revealed an increase of DHA in the retina, particularly in the photoreceptor layer, around the optic nerve, regardless lipid formula. Our quantitative data revealed a better integration of DHA, particularly DHA-containing phosphatidylcholine, in the retina, when EPA is provided esterified on phospholipids, and DHA is provided on both, phospholipids and triglycerides. All the supplemented diets allowed an increase in very long chain-PUFAs in the retina
Fouché, Christophe. "Présentation des différentes statines et utilisation clinique." Paris 5, 2005. http://www.theses.fr/2005PA05P208.
Sion, Adeline. "Evaluation des taux plasmatiques de certaines cytokines et des lipides au cours de l'infection par le virus de l'immunodéficience humaine." Bordeaux 2, 1993. http://www.theses.fr/1993BOR2PE75.
Fournis, Véronique. "Polymorphisme de l'apoliprotéine A-IV humaine (codons 347 et 360) : moyens d'analyse génotypique ; fréquence et relations avec les paramètres du bilan lipidique chez le sujet diabétique." Bordeaux 2, 1997. http://www.theses.fr/1997BOR2P073.
Merzouk, Hafida. "L'hypotrophie et la macrosomie du nouveau-né à terme s'accompagnent de perturbations importantes du métabolisme des lipides et des lipoprotéïnes." Dijon, 1999. http://www.theses.fr/1999DIJOS010.
Beauchène, Dominique. "Diabète sucré et dyslipidémie à propos d'une étude portant sur 256 familles de diabétiques non insulino-dépendants." Paris 5, 1994. http://www.theses.fr/1994PA05P166.
Bouvelle, Anne. "Hypercholestérolémies, dyslipidémies : traitements et prévention." Paris 5, 1992. http://www.theses.fr/1992PA05P064.
Groizeleau, Dominique. "Hypertriglycéridémie de type I et pancréatite aigue͏̈ : revue de la littérature à propos d'une observation." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2M022.
Xu, Elaine Meng. "Role of ceacam1 and shp1 in the regulation of insulin sensitivity and hepatic glucose and lipid metabolism." Doctoral thesis, Université Laval, 2012. http://hdl.handle.net/20.500.11794/23713.
L’obésité et le diabète de type 2 (T2D) sont étroitement associés à la résistance à l’insuline, une maladie métabolique qui se développe suite à un défaut causé par une réduction de la signalisation de l’insuline et de sa clairance. Afin de comprendre la pathogenèse de la résistance à l’insuline plusieurs molécules qui régulent les voies de signalisation ainsi que la clairance sous contrôle du récepteur à l’insuline ont été étudiées, incluant la protéine tyrosine phosphatase (PTP) SHP1 et la molécule carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1 or CC1) qui est régulée en aval sous le contrôle de SHP1. Les nombreuses isoformes de CC1 contribuent à différentes fonctions cellulaires. Dans le foie, l’isoforme CC1-L, qui est phosphorylée sur tyrosine (Tyr), joue un rôle métabolique essentiel dans la régulation de la clairance de l’insuline et dans la suppression de l’activité de la synthase des acides gras (FAS). Nous avons démontré que des souris invalidées pour CC1 (Cc1-/-) sous un régime standard faible en gras (SD) développent néanmoins une importante stéatose hépatique qui est démontré par une augmentation de triglycérides, de cholestérol total ainsi que de cholestérol estérifié dans le foie. Sous un régime contenant 55% de gras (HFD) ces mêmes souris démontrent une prédisposition au développement de la stéatose et dysfonction hépatique induite par le régime, indiqués par une accumulation de lipides hépatiques et une augmentation d’enzymes marqueurs de dommage hépatique dans la circulation. La stéatose hépatique dans la souris Cc1-/- est liée à une augmentation significative d’importantes enzymes lipogéniques et de la synthèse du cholestérol qui sont régulés suite à une augmentation de l’activité nucléaire des facteurs de transcription Srebp1c et Srebp2. Comparées aux souris contrôle sauvages (WT) les souris CC1-/- ont démontré une réduction de la clairance de l’insuline, une intolérance au glucose, une résistance à l’insuline hépatique et une augmentation d’expression des activateurs transcriptionels hépatiques PGC-1 et FoxO1. L’absence de CC1 a aussi exacerbé l’intolérance au glucose et la résistance à l’insuline hépatique induite par le régime à haute teneur de gras mais la clairance de l’insuline n’était pas diminuée dans les souris Cc1 -/-. Nos donnés indiquent que CC1 est un important régulateur de la lipogénèse hépatique et que les souris CC1-/- sont prédisposées à développer une stéatose hépatique qui mène à une résistance à l’insuline hépatique et des dommages dans le foie qui sont surtout évidentes sous un régime riche en lipides. Une importante Tyr phosphatase de CC1 est SHP1. Précédemment nous avons démontré que SHP1 est un important régulateur de l’homéostasie du glucose et de la clairance de l’insuline par le foie, cependant son rôle dans l’obésité liée au diabète reste méconnu. Nous rapportons ici que l’expression de SHP1 est significativement augmentée dans les tissus métaboliques de souris obèses sous régime HFD. Nous avons généré des souris invalidées pour SHP1 spécifiquement dans les hépatocytes (Ptpn6H-KO) pour investiguer le rôle de SHP1 dans le développement de la résistance à l’insuline et de la stéatose hépatique. Sous régime HFD les souris Ptpn6H-KO deviennent aussi obèses que les souris non invalidées pour SHP1 (Ptpn6f/f). Malgré ceci les souris Ptpn6H-KO démontrent une amélioration de la glycémie à jeun et une protection contre la résistance à l’insuline induite par l’obésité qui est confirmée par la suppression de la synthèse de glucose hépatique ainsi qu’une amélioration de l’activation du récepteur pour l’insuline avec une augmentation concomitante des voies de signalisation Akt. Il est aussi possible que la clairance de l’insuline accrue qu’on observe dans les souris Ptpn6H-KO soit due à une augmentation de la phosphorylation sur tyrosine de CC1. Les souris obèses Ptpn6H-KO montrent une augmentation de stéatose hépatique qui est le résultat de 1) une augmentation de lipogénèse hépatique associée à une augmentation importante de l’activité et de l’expression de SREBP-1 et des enzymes lipogéniques en aval FAS et ACC, 2) une augmentation de la captation postprandiale des acides gras qui est possiblement liée à une augmentation de l’expression du gène et de l’activité nucléaire de PPARγ, 3) une diminution de la sécrétion des triglycérides et de l’apolipoprotéine B sous le forme de lipoprotéines de très basse densité (VLDL). Étonnamment, malgré le niveau élevé de stéatose hépatique, le profil inflammatoire dans le foie des souris Ptpn6H-KO était similaire ou même amélioré comparé aux souris contrôles Ptpn6f/f et ceci était accompagné d’une diminution de dommage hépatocellulaire. Ces résultats démontrent que SHP1 est un nouveau médiateur de la résistance à l’insuline dans les hépatocytes et contribue à la détérioration du métabolisme du glucose induite par l’obésité. Chez la souris Ptpn6H-KO la stéatose hépatique induite par le régime suggère par ailleurs un autre rôle de SHP1 dans la régulation du métabolisme hépatique des lipides. Malgré le fait que CC1 et SHP1 se retrouvent dans le même complexe que Cdk2 et le récepteur de l’insuline, ils jouent des rôles opposés, CC1 étant un régulateur positif et SHP1 un régulateur négatif de la clairance de l’insuline. Ceci est en accord avec la régulation hépatique par le glucose des voies de signalisation de l’insuline pour ces deux molécules car les souris Cc1-/- démontrent une détérioration du métabolisme du glucose et de la signalisation de l’insuline alors que les souris Ptpn6H-KO démontrent une amélioration. Notre observation de stéatose hépatique chez ces deux modèles animaux suggère que CC1 et SHP1 limitent la synthèse et l’entreposage des lipides hépatiques de façon dépendante ou indépendante de la signalisation de l’insuline. Les résultats de ces études utilisant des modèles invalidés pour CC1 ou SHP1 révèlent des mécanismes du contrôle de la synthèse de glucose hépatique et du métabolisme des lipides qui sont très complexes et distincts. En plus ces résultats nous apportent une compréhension importante de la régulation hépatique de l’action et de la clairance de l’insuline.
Obesity and type 2 diabetes mellitus (T2D) are tightly associated with a common link, insulin resistance, a metabolic disorder developed from defective insulin action involving impaired insulin signaling and clearance. To investigate the pathogenesis of insulin resistance, many molecules modulating its signaling pathways as well as insulin receptor-mediated insulin clearance have been studied, including the protein tyrosine phosphatase (PTP) SHP1 and its regulated downstream molecule carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1 or CC1). CC1 in multiple isoforms contributes differentially to various cellular functions, the tyrosine (Tyr)-phosphorylated isoform of CC1 (CC1-L) is known to play an essential metabolic role in the hepatic regulation of insulin clearance and insulin-mediated acute inhibition of fatty acid synthase (FAS) activity. We have found that CC1-deficient (Cc1-/-) mice on standard diet (SD) already develop spontaneous hepatic steatosis with significantly elevated accretion of triglyceride (TG), total and esterified cholesterol. When challenged with a 55% kcal high-fat diet (HFD), these mice show greater susceptibility to the development of diet-induced hepatic steatosis and dysfunction, indicated by higher hepatic lipid content and serum levels of hepatic enzymes as markers of liver damage. Hepatic steatosis in the Cc1-/- mice is linked to a significant increase of key lipogenic (FAS, ACC) and cholesterol synthetic (HMGCR) enzymes, which is a result of increased nuclear activity of their positive gene transcription factors Srebp1c and Srebp2. Compared to their wild-type (WT) littermate controls, Cc1-/- mice exhibited impaired insulin clearance, glucose intolerance, liver insulin resistance, and elevated hepatic key gluconeogenic transcriptional activators Pgc1 and FoxO1. Lack of CC1 also exacerbated the HFD-induced glucose intolerance and hepatic insulin resistance, while insulin clearance was not further deteriorated. These data demonstrate that CC1 is a key regulator of hepatic lipogenesis and that Cc1-/- mice are predisposed to liver steatosis, leading to hepatic insulin resistance and liver damage, particularly when chronically exposed to dietary fat. An important Tyr phosphatase of CC1, SHP1, has been found previously by our lab to regulate glucose homeostasis and liver insulin clearance, but its potential implication in obesity-linked insulin resistance and hepatic steatosis has not yet been examined. We hereby report that SHP1 expression is significantly upregulated in metabolic tissues of HFD-fed obese mice. We have also further investigated the role of hepatocyte SHP1 in promoting insulin resistance and hepatic steatosis by generating hepatocyte-specific SHP1 knockout mice (Ptpn6H-KO). Upon HFD feeding, Ptpn6H-KO mice develop obesity as their Ptpn6f/f littermates. With consistently improved fasting glycemia, these mice are protected from obesity-induced liver insulin resistance as revealed by normalized insulin suppression of hepatic glucose production and hepatic insulin signaling with improved activation of insulin receptor and downstream signaling through Akt. More rapid insulin clearance in Ptpn6H-KO mice due to heightened CC1 tyrosine phosphorylation is also a possible contribution to the improved insulin action. Unexpectedly, obese Ptpn6H-KO mice exhibit enhanced hepatic steatosis. In detailed mechanisms, this is a result of 1) augmented hepatic lipogenesis, marked by upregulated activity and expression of SREBP-1 as well as the downstream regulated lipogenic enzymes such as FAS and ACC, 2) increased postprandial fatty acid uptake, possibly linked to the upregulation of PPAR gene expression and nuclear activity, and 3) decreased postprandial TG output in apolipoprotein B (ApoB)-associated lipoprotein particles, i.e. very low density lipoprotein (VLDL). More interestingly, the steatotic livers of these Ptpn6H-KO mice display comparable or even reduced level of inflammation accompanied by significantly less hepatocellular damage than that in their Ptpn6f/f counterparts. These results present hepatocyte SHP1 as a novel mediator of insulin resistance compromising hepatic glucose metabolism in diet-induced obesity. The enhanced diet-induced hepatic steatosis in Ptpn6H-KO mice provides a new role for SHP1 in liver lipid metabolism and further supports the bifurcation of insulin signaling in the regulation of hepatic glucose and lipid homeostasis or also confirms a possible disconnection between hepatic regulation of glucose and lipid metabolism. Although both CC1 and SHP1 are found in the same complex with Cdk2 and insulin receptor to regulate insulin clearance, they play opposing roles as CC1 is the positive regulator and SHP1 being the negative one. This is in accordance with the hepatic glucoregulation of insulin signaling for both molecules, since Cc1-/- mice show impaired glucose metabolism and insulin signaling whereas Ptpn6H-KO mice exhibit improvement. Interestingly, our observation of hepatic steatosis in both animal models, though with different characteristics, suggests that both CC1 and SHP1 limit hepatic lipid synthesis and storage, dependent or independent of insulin signaling. Findings from these studies using animal models lacking CC1 and SHP1 reveal complex and differential regulatory mechanisms of hepatic glucose and lipid metabolism, and they also provide important understanding of the hepatic regulation of insulin action and clearance.
Dorent, Anne. "Les marqueurs du tabagisme dans une population dyslipidémique." Paris 5, 1990. http://www.theses.fr/1991PA05P095.
Dollet, Lucile. "Fonctions adipocytaires de la seipine : mécanismes physiopathologiques de la Lipodystrophie Congénitale de Berardinelli-Seip (BSCL)." Nantes, 2015. https://archive.bu.univ-nantes.fr/pollux/show/show?id=d4934403-af99-4cf7-9237-d0314bc9d6e6.
Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare genetic disease characterised by an almost complete lack of adipose tissue from birth, associated with severe insulin resistance. BSCL is caused by mutations occurring in the gene encoding seipin (BSCL2) in 50% of cases. Seipin function remains largely unknown at this time. Here, we showed that seipin deficiency impaired white adipocyte differentiation, which can be restored by thiazolidinediones (TZD). In our Bscl2 knock-out lipodystrophic mice model (Bscl2-/-), TZD treatment increased adipose tissue mass and adiponectin and leptin secretion, and consequently improved insulin resistance. To better characterize metabolic consequences of lipodystrophy, we studied Bscl2-/- mice adaptative responses to cold exposure or prolonged fasting. We highlighted a central role of white adipose tissue dysfunction in the metabolic inflexibility of Bscl2-/- mice. Beyond its role in adipocyte differentiation, we reported that seipin is essential for mature adipocyte. Seipin knock-down in differentiated adipocytes triggered cellular stress leading to adipocyte apoptosis, showing a role of seipin in adipocyte maintenance. Fibroblast growth factor 21 (FGF21) prevented seipin deficient adipocytes from degradation and preserved residual adipose tissue in vivo. In conclusion, our results highlight a role of seipin in both adipogenesis and mature adipocyte maintenance. Although the exact function of seipin remains to decipher, our results allow a better understanding of lipodystrophy due to seipin deficiency, and show beneficial effects of therapeutic approaches targeting adipose tissue
Fergani, Anissa. "Altérations métaboliques dans la sclérose latérale amyotrophique." Université Louis Pasteur (Strasbourg) (1971-2008), 2007. http://www.theses.fr/2007STR13132.
Bernard, Lucie. "Rôle de FAT10 dans la sénescence des hépatocytes et le développement de la NASH." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2023/2023ULILS039.pdf.
The accumulation of senescent hepatocytes has been identified as a key factor in the progression of non-alcoholic fatty liver diseases (NAFLDs), which correspond to a spectrum of chronic liver pathologies, ranging from simple steatosis to the development of non-alcoholic steatohepatitis (NASH), cirrhosis or even hepatocellular carcinoma (HCC). However, the mechanisms and actors involved in the regulation of senescence during NASH are still poorly described. The objective of this thesis was therefore to study the mechanisms controlling hepatocyte senescence during the development of NASH. Using transcriptomic and protein analyses, we have shown in the livers of patients and mice that the protein FAT10 (human leukocyte antigen-F Adjacent Transcript 10), also called UBD (Ubiquitin D), is induced during NASH. However, FAT10 is an ubiquitin-like protein that interacts with different partners playing a role in metabolism and senescence, we therefore hypothesized that FAT10 could be involved in the development of NASH, as well as in the induction and spread of hepatocyte senescence. First, we showed in the livers of NASH patients a positive correlation between the expression of FAT10 and the severity of the disease. Conversely, FAT10 expression decreases when the disease regresses. We showed specifically in hepatocytes of NASH mice that the expression of Fat10 negatively correlates with lipid metabolism pathways, and that interestingly, the decrease of Fat10 expression in NASH mice hepatocytes decreases hepatic steatosis, by reducing the size and number of lipid droplets. Secondly, we showed a positive correlation between the expression of FAT10 and of senescence genes in the livers of NASH patients. This correlation is found specifically in hepatocytes in mice. Furthermore, in this mouse model of NASH, Fat10 expression positively correlates with liver SA-β-Gal (Senescence Associated-β-Galactosidase) activity. In vitro, the induction of senescence in human hepatocytes by an irradiation or a treatment with H2O2 induces FAT10 protein as a SASP (Senescence Associated Secretory Phenotype) actor. Interestingly, FAT10 inhibition in this model promotes the induction and propagation of senescence, through an increase of SA-β-Gal activity, an induction of SASP genes, an accelerated cell proliferation arrest, an induction of the DNA damage response system and a greater accumulation of lipid droplets. Conversely, stable overexpression of FAT10 in senescent hepatocytes accelerates the loss of senescent status (decreased SA-β-Gal activity), and promotes the senescence escape and the acquisition of a pro-cancerous phenotype. In the end, all of these data suggest that the induction of FAT10 within hepatocytes during the development of NASH promotes the progression of the disease, on one hand by altering lipid metabolism within steatotic hepatocytes, and on the other hand by gradually promoting the escape of senescent hepatocytes, which could lead to the development of HCC
Clément, Laurence. "Effets des lipides sur le contrôle nerveux de l'homéostasie glucidique chez le rat : aspects cellulaires et moléculaires." Paris 11, 2002. http://www.theses.fr/2002PA11T025.
Type 2 diabetes represents 90 to 95% of all cases of diabetes and is characterised by insulinresistance along with an alteration pancreatic β-cell insulin secretion, resulting in chronic hyperglycemia. The mechanisms responsible for such alterations are not fully understood. In a preliminary study, we found that β-cell dysfunction partly results from a deleterious effect of free fatty acids (FFA) on the sympathetic nervous system. The aim of this work was to determine the molecular and cellular mechanisms implicated in the alteration of nervous regulation of glucose homeostasis by lipids. In Wistar rats infused intracerebroventricularly with a triglyceride emulsion and heparin, we found that lipids may act on the central nervous system (CNS) to induce an increase in glucose-induced insulinsecretion (GIIS). As shown by the pancreatic turnover of norepinephrine, the effect of lipids is probably mediated by a decrease in the sympathetic output to the pancreas. We also found a decreased liver insulin sensitivity in these rats, associated with a hypercorticosteronernia. Consequently, our aim was to determine the molecular mechanisms les mécanismes cellulaires implicated in the action of lipids on the CNS. Microarray studies of the hypothalamic RNA of these rats showed that lipids induce transcriptional changes of specifie genes, which could account for the metabolic alterations, such as the leptine receptor. We then focused on the binding characteristics of pancreatic β-cell α2A adrenergic receptors in response to elevated circulating FFA levels. These receptors have been shown to mediate inhibition of GIIS by norepinephrine. We found a decreased number and an increased affinity of these receptors. We also found that FFA induce changes in islet membrane phospholipidic composition, which may account for the increased affinity of the receptors. We conclude that these data suggest that the diabetogenic effect of FFA may not only result from changes in glucose metabolisme, but also from alterations in the sympathetic nervous output to the pancreas, and to neurophysiologie modifications, probably mediated by changes in hypothalamic activity
Kuznetcova, Daria. "Development and characterization of chia (Salvia hispanica L.) plant-derived products as natural bioactive compounds." Electronic Thesis or Diss., Université de Lorraine, 2020. http://www.theses.fr/2020LORR0266.
Omega-3 polyunsaturated fatty acids (PUFA) are important for nutrition and health, by virtue of their importance in lipid homeostasis, and the fact that PUFA deficiencies can increase risk of metabolic syndrome, cardiovascular and neurodegenerative diseases. Chia (Salvia hispanica L.) seeds are rich in PUFA (80%) and contain the highest known levels in plants of the essential omega-3 fatty acid, alpha-linolenic acid (ALA). High degree of unsaturation in edible oils can reduce oxidative stability causing a loss of nutritional value. Nanotechnology can be used to improve chia seed oil quality and safety, increase bioavailability, and expand the scope of applications. Towards this goal, our objective was to prepare and characterize chia seed lipids in the form of nanoliposomes (NL) and nanoemulsions (NE), and to evaluate their potential use as bioactive products. The first step was to characterize lipid fractions. Lipids were extracted from the French ORURO variety of chia seeds using modified Folch method. Ten fatty acid species and six phospholipid (PL) classes were identified in chia seed lipid extract by gas chromatography and LC-MS, respectively, with the highest level of fatty acids being ALA (62%). The presence of a solid residue was detected following evaporation of the solvent to obtain chia seed oil. Analyses by thin layer chromatography and LC-MS demonstrated that this residue contained the polar lipids including PL that were no longer in the chia oil after removal of solvent by evaporation. NE were prepared from chia seed oil and the chia PL-rich solid residue, and NL from the PL-rich solid residue. Physicochemical characterization including analysis of the polydispersity index (PDI), size, and zeta-potential indicated that both NE and NL were monodispersed solutions of stable (low negative zeta potential) particles with a size between 104-118 nm. These preparations were spherical and multilayered (transmission electron microscopy) and remained stable even 5 days after preparation. In addition, enzymatic assay confirmed PL content in both NE and NL. MTT cell viability assay showed little to no cell toxicity (up to 150 µg/mL NE or NL) following 24 h incubation with cultured hepatocytes, neurons, and astrocytes. In conclusion, these results demonstrate the feasibility of using chia lipids for the preparation of stable non-toxic omega-3 PUFA rich NL and NE, which represent potential bioactive vectors for both preventive and therapeutic applications in human health
Pitel, Séverine. "Intérêts de supplémentations nutritionnelles en acides gras polyinsaturés dans la neuropathie diabétiqueEtudes clinique et expérimentale." Aix-Marseille 2, 2007. http://www.theses.fr/2007AIX20678.
Lukaszewski, Marie-Amélie. "Effets d'une dénutrition maternelle prénatale sur la régulation de l'homéostasie énergétique chez la descendance mâle adulte : focus sur l'hypothalamus et le tissu adipeux." Thesis, Lille 1, 2011. http://www.theses.fr/2011LIL10133/document.
Epidemiological studies have shown that maternal undernutrition during pregnancy (MU) leads to intrauterine growth retardation and may predispose individuals to the development of metabolic syndrome. In order to better understand the underlying mechanisms, we have developed a model of prenatal maternal 70% food-restricted diet throughout gestation in pregnant female rats called FR30. Our results show that MU increases the vulnerability to some metabolic syndrome features in adult male rat offspring such as mild hypertension, hyperleptinemia without obesity, hypercorticosteronemia, impaired glucose intolerance and hyperphagia and subtle alterations of POMC hypothalamic neurons projections. Our goal was then to identify tissue mechanisms programmed by MU in FR30 adult male offspring hypothalamic-adipose axis (HA). Based on the developmental origins of the metabolic syndrome, we attempted to heighten visible and/or silent metabolic alterations observed under standard diet by feeding FR30 rats a high fat (HF) diet since the weaning. Although MU does not worsen the metabolic syndrome features induced by postnatal HF feeding, FR30 adult rats gain more weight, exhibit greater body fat content, a rise of serum leptin levels and a blunted increase of corticosterone levels. FR30 MU does not significantly affect the hypothalamic mRNA levels whereas it leads to marked gene expression variation in WAT in depot-specific and diet-specific manners. Our results suggest that the HA tissue axis is one of the key targets of MU fetal programming in adult male rat offspring
Rigoard, Philippe. "Caractérisation physiopathologique, moléculaire et métabolique de la jonction neuromusculaire et du nerf périphérique après lésion du système nerveux central." Poitiers, 2007. http://www.theses.fr/2007POIT1405.
Badiou, Stéphanie. "Dyslipidémie chez le sujet infecté par le virus de l'immuno-déficience humaine : caractérisation, influence des traitements antirétroviraux et approche thérapeutique." Montpellier 1, 2003. http://www.theses.fr/2003MON13512.
Merlin, Jean-François. "Régulation de la biosynthèse des acides gras polyinsaturés chez le rat spontanément hypertendu SHR : influence d'une inhibition pharmacologique de la Delta-6 désaturase et effets d'un régime enrichi en isomères conjugués de l'acide linoléique (CLA)." Dijon, 2006. http://www.theses.fr/2006DIJOS011.
Arterial hypertension (AHT) frequently coexists with numerous metabolic abnormalities, particularly abnormalities of polyunsaturated fatty acids (PUFA) composition. Delta-6 desaturase (D6D) is the key step enzyme of hepatic PUFA biosynthesis. D6D is partially inhibited during AHT in spontaneously hypertensive rat (SHR). The consequences of such an inhibition of PUFA biosynthesis on AHT and on hepatic lipid metabolism remain to be investigated. We firstly generated a pharmacological chronic D6D inhibition. This treatment, in addition to block PUFA biosynthesis, exacerbates lipid abnormalities usually shown in SHR, without changing blood pressure. Then, we performed a CLA supplementation (cis-9 trans-11, or trans-10 cis-12 linoleic acids) in SHR. Each isomer activates D6D and corrects some of the lipid abnormalities reported in SHR, while slowing AHT evolution. Moreover, PPARγ and SREBP1c transcription factors could be involved in such SHR hepatic metabolic dysfunctions
Larrieu-Charpentier, Brigitte. "Méthodes d'épuration extra-rénale et perturbations lipidiques chez l'insuffisant rénal chronique." Paris 5, 1990. http://www.theses.fr/1990PA05P188.
Podechard, Normand. "Rôles des hydrocarbures aromatiques sur la régulation de l’interleukine 8 et de la protéine Niemann-Pick type C1 dans les macrophages humains en culture primaire et leurs effets sur l’accumulation de lipides dans différents modèles cellulaires." Rennes 1, 2008. http://www.theses.fr/2008REN1S136.
Romon, Monique. "Influence de l'heure du repas sur les réponses métaboliques et hormonales : application aux perturbations associées au travail poste." Nancy 1, 1997. http://www.theses.fr/1997NAN10236.
Siraz, Sachendra. "Utilisation des inhibiteurs de l'hydroxy-méthyl-glutaryl co-enzyme A réductase chez les sujets âgés. Efficacité et tolérance." Bordeaux 2, 1996. http://www.theses.fr/1996BOR2M023.
Robelin, Laura. "Analyse de la composition en acides gras des lipides dans la sclérose latérale amyotrophique : implications dans le processus pathologique." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ095/document.
ALS is a fatal neurodegenerative condition characterized by the selective loss of upper and lower motor neurons. The disease is also characterized by alterations of energy homeostasis and lipid metabolism. The objective of this PhD work was, first, to identify changes in fatty acid composition of lipids in blood of ALS patients, as potential diagnosis and prognosis biomarkers of the disease. The second goal was to modulate these changes, by nutritional approaches, in order to better understand the involvement of an altered lipid metabolism in the pathological process. Our results showed that high levels of monounsaturated fatty acid (MUFA), as well as low levels of polyunsaturated fatty acids (PUFA), are associated with a better prognosis. The analysis of the effects of a modified fatty acid composition in both pathological and lesion models of denervation, has confirmed implication of the antagonistic relationship between MUFA and PUFA in the neurodegenerative process. This work suggests a cautious usage of fatty acids in therapeutic approaches targeting ALS
Torres, Romero Ismael. "Dynamics of lipid reserves in the model microalga Chlamydomonas reinhardtii." Thesis, Aix-Marseille, 2020. http://www.theses.fr/2020AIXM0023.
Large research efforts have been put to domesticate microalgae for production of sustainable biofuels and other valuable compounds. Triacylglycerols (TAGs, or oils) and starch are the major forms of carbon storage in green algal cells. However, the conditions used to enrich microalgal biomass with these carbon reserves severely undermine cell growth therefore compromising productivity. An economically viable production of lipids from microalgae requires a deeper and integrated understanding of lipid synthesis, storage and cell division. The goal of this thesis is to dissect the connection between cell division and carbon storage, and to understand the biogenesis of the lipid droplet (LD), the major subcellular site where TAGs are stored. Toward this goal, we first investigated the incompatibility between carbon storage and cell growth. By characterizing genetically and biochemically mutants of Chlamydomonas reinhardtii deficient in CDC5 protein, we demonstrate its implication in the cell cycle and show that a slowdown in cell division entails a diverted flow of energy and carbon towards the synthesis of TAGs and starch without arresting cell growth. Secondly, we identified and characterized a putative α/β-fold hydrolase (CrABHD1), one of the major proteins associated to LDs in Chlamydomonas. The CrABHD1 recombinant protein purified from Escherichia coli hydrolyzes lyso-DGTS to produce a free fatty acid and a glycerol-N,N,N-trimethylhomoserine (GTH). We have discovered a novel LD-associated protein and demonstrated its capacity in increasing lipid content in microalgae, which should have important implications for a greener bioeconomy
Braud, Laura. "Effets lipotropes des molécules antioxydantes du thé (Camellia sinensis)." Thesis, Toulon, 2015. http://www.theses.fr/2015TOUL0014/document.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrializedcountries because being strongly associated with the development of metabolic syndrome and relateddyslipidemia. To date, the mechanisms of pathology remain poorly defined and available therapeutic meanshave moderate efficacy. Epidemiological studies have reported a beneficial effect of tea consumption in thefight against liver disorders and cardiovascular risk factors such as dyslipidemia. However, the mechanismsby which a blend of green tea, oolong tea and Pu-erh tea, Hao Ling tea, reduces fatty liver and dyslipidemiaremain unknown. Therefore, the objective of this thesis was to evaluate the effects and mechanisms of actionof Hao Ling tea on NAFLD and dyslipidemia, through two approaches, one on cellular model and the other onanimal model. Our results show that Hao Ling tea reduces the hepatic lipogenesis in vitro and in vivo and thusattenuates steatosis induced by a high fat-high sucrose diet in a rat model. We observed that this tea improvesthe blood lipid profile by increasing plasma HDL levels. We were also able to highlight that tea ownsantioxidant and hepato-protective properties to counteract an inducer of oxidative stress in vitro and todecrease lipid peroxidation in vivo. Finally, we have shown that the oxidative stress per se resulted in anaccumulation of intracellular lipid in isolated hepatocytes and that the tea, due to its antioxidant properties,prevented this phenomenon. The Hao Ling tea is a good nutritional approach in preventing NAFLD and tomaintain LDL/HDL ratio
Lecomte, Manon. "Les lipides polaires laitiers modulent l’absorption lipidique et la lipémie postprandiale : conséquences métaboliques chez la souris." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1012.
Metabolic diseases are characterized by an altered lipid metabolism and metabolic inflammation. Numerous food products contain polar lipid (PL) emulsifiers that could impact these risk factors. We evaluated the impact of using PL from milk (MPL) (i) acutely on lipid digestion and postprandial lipemia and (ii) in the longer term in addition to a high fat diet on adiposity and adipose tissue inflammation. We compared MPL to soybean PL (SPL) that is currently the main commercial source of PL.In mice, an emulsion stabilized by MPL results in a more rapid postprandial lipemia than an emulsion stabilized by SPL, with an early increase in lipemia and a faster clearance. Differences in lipemia can originate from differential kinetics of lipid hydrolysis in the mouse gut, as an increase intestinal TG hydrolysis is observed in vitro. Moreover, early MPL-derived chylomicrons are smaller than SPL-derived chylomicrons. In the longer term, compared with HF diet, HF-SPL diet increases hepatic lipids, white adipose tissue (WAT) mass, with larger and more numerous adipocytes and increases expression of pro-inflammatory adipokines. This is not observed with HF-MPL diet despite similar dietary intakes. HFP-MPL mice have a lower expression in WAT of marker of macrophage infiltration and more numerous goblet cells in the colon, suggesting an improved gut barrier function with this diet.Postprandial lipemia in mice can be modulated by emulsifying with MPL compared with SPL, partly through differences in chylomicron assembly, and intestinal TG hydrolysis rate. Moreover unlike SPL, MPL in a high fat diet do not induce WAT hypertrophy and inflammation
Ling, Yiin. "Phenotyping and understanding constitutional thinness : demonstrating and understanding specific energy metabolism through overfeeding study." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSES023.
Constitutional thinness (CT) is a non-pathological state of underweight associated with normal nutritional and hormonal profiles and without eating disorders. We previously conducted a four-week fat overfeeding study showing weight gain resistance in CT women and one of our main results was the identification of an energy gap: a positive energy balance (higher energy intake than energy expenditure). A second overfeeding study was designed and conducted with a daily surplus of 600 kcal (a bottle of Renutryl©) to confirm the energy gap and propose mechanistic hypothesis. We first clearly established the existence of CT on both genders and reproduced the paradoxical positive energy gap in a larger sample. We found smaller adipocytes in CTs, with higher mitochondrial activity via β-oxydation, and increased mitochondrial number. Overexpressed genes related to positive metabolic outcomes and triglyceride biosynthesis were found in CT’s adipose tissue. Our findings suggest an augmented futile lipid cycling and therefore an important role for mitochondria in mediating sustained CT’s low bodyweight. In muscle, protein-energy overfeeding paradigm confirmed a blunted skeletal muscle energy metabolism in CTs, associating a positive energy balance and a positive nitrogen balance and a high protein consumption profile. Finally, this blunted energy metabolism of CTs’ skeletal muscle could also partly explain the positive energy gap and the relative resistance to lean mass gain in the present protein-energy overfeeding study
Thöni, Gilles. "Anomalies métaboliques du patient infecté par le Virus de l'immunodéficience humaine (VIH) sous multithérapie antirétrovirale : vers une individualisation de la prise en charge par l'entraînement aérobie." Montpellier 1, 2002. http://www.theses.fr/2002MON14007.
Blanchard, Géraldine. "Etude des lipoprotéines chez le chat : application à la lipidose hépatique induite : effets d'une supplémentation en L-carnitine durant la phase d'induction de l'obésité." Paris, Institut national d'agronomie de Paris Grignon, 2002. http://www.theses.fr/2002INAP0046.
Mellouk, Namya. "Etude de trois adipocytokines, adiponectine, visfatine et chémérine au niveau plasmatique et dans plusieurs tissus métaboliques et reproducteurs de différentes espèces." Thesis, Tours, 2018. http://www.theses.fr/2018TOUR4007.
This thesis is focused on the study of three adipokines (adiponectin, visfatin and chemerin) in species that develop abnormalities of energy metabolism associated with reproductive disorders. Our results have shown some diet effects on the lipid and carbohydrate metabolisms and in a less extend, on the reproductive functions in dairy cows and broiler hens. These effects were partly associated with the expression profiles of adiponectin, visfatin and chemerin. In addition, we have demonstrated overexpression of the chemerin/CMKLR1 system in follicular fluid and in ovarian cells of patients with polycystic ovarian syndrome, with or without obesity. First, these findings reveal the possibility of considering these adipokines as potential biomarkers for evaluating growth, fattening status and fertility in agricultural farms. On the other hand, they suggest a potential involvement of chemerin in the regulation of ovarian functions in women
Ferro, Fabio. "Régulation des canaux ioniques cardiaques par les acylcarnitines." Thesis, Tours, 2012. http://www.theses.fr/2012TOUR3315/document.
Several diseases can cause either an increase or a decrease in the rate of fatty acids (FAs) and their derivatives circulating, including acyl-carnitines (AC). This change is suspected as being the cause of major cardiac electrical perturbations. We have shown that long-chain AC (LCAC) modulate specifically by the extracellular side the hERG channel, regulating its current amplitude and kinetics. All AC tested had no effect when applied intracellularly. Carnitine and medium chain AC had no effect on hERG. LCAC does not modulate IK1 and IKS. Cav1.2 channel is modulated by C16 and C16-CAR in line HEK293-ICaL and rat cardiomyocytes. In physiological conditions there exists a strict link between energy metabolism and cardiac electrical activity which causes a permanent modulation of hERG channel by the LCAC. Regulation by the LCAC of the hERG channel and maybe ICaL, could participate in the electrical disturbance causing the onset of cardiac arrhythmia found in certain diseases
Fagot-Campagna, Anne. "Anomalies lipidiques : rôles sur l'incidence du diabète de type 2 et de ses complications micro et macro vasculaires." Paris 11, 1998. http://www.theses.fr/1998PA11T034.
Lipid abnormalities (decreased HDL and HDL2 cholesterol, increased VLDL triglycerides and small and dense LDL, glycation, oxidation) are an important component of the insulin-resistance syndrome that precedes type 2 diabetes. Free fatty acids play an aggravating and potentially initiator role in the development of type 2 diabetes. HDL cholesterol may have a protective effect in women only, which may imply a role of sexual hormones. Lipids have a potential effect on the development of micro-vascular complications. Their role on retinopathy has not been well studied. LDL cholesterol and especially its qualitative modifications may have deleterious effects on nephropathy, whereas HDL cholesterol may be protective in women only. Lipids play a major role in the development of macro-vascular complications. LDL and HDL cholesterol and their qualitative modifications are recognized risk factors. Triglycerides may also be an independent risk factor for cardiovascular diseases in type 2 diabetes, and free fatty acids may have deleterious effects on cardiac function and blood pressure. In conclusion, the lipid abnormalities associated with type 2 diabetes bring a fatal combination. As compared with glucose control, lipid abnormalities lead a minor but potential role in the development of micro-vascular complications, but a major role in the development of macro-vascular complications, which correspond to the first cause of mortality. Hypolipidemic treatment, together with other preventive measures of cardiovascular diseases, should probably be ranked first, and may be before diabetes control, during type 2 diabetes care
Florens, Nans. "Modifications post-traductionnelles des lipoprotéines de haute densité (HDL) et risque cardio-vasculaire dans l’insuffisance rénale chronique." Thesis, Lyon, 2020. http://www.theses.fr/2020LYSE1034.
Cardiovascular complications remain the main problem in chronic kidney disease (CKD) but all the reasons of this risk are not fully understood. there is an addition of traditional risk factors and uremia-related ones. Among the latter, the generation of post-translational modifications of HDL could play a role. In this work, we highlighted an excess of carbonylation by 4-HNE onto the protein part of HDL in CKD in a rabbit model of CKD and in hemodialysis and peritoneal dialysis patients. This carbonylation by 4-HNE is responsible for ablunted anti-aggregant properties of HDL mediated by a CD36-dependant pathway. We also showed that the proteome of HDL from non diabetic hemodialysis patients is deeply modified and that there were several post-translational modifications onto the protein cargo of these HDL. The generation of carboxylate-methyl-lysine from non-enzymatic glycation processes was the main modification in our patients. The origin of such glycation could be from a favorable chemical environment but a potential load from hemodialysis fluids should be addressed
Schmitt, Florent. "Rôle de la stéaroyl-coenzyme A désaturase 1, une enzyme de synthèse des acides gras mono-insaturés, dans un modèle transgénique d’étude de la Sclérose Latérale Amyotrophique." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ085/document.
Amyotrophic lateral sclerosis is a neurodegenerative disease, associated with metabolic dysfunction. Alteration of lipid metabolism has been documented in ALS patients and animal models, and could participate to the first pathological steps of the disease. The objective of this thesis was to study the role of stearoyl-CoA desaturase 1 (SCD1), a key enzyme of lipid metabolism, in ALS. By studying the profile of peripheral fatty acids in an animal model of ALS, the SOD1 mice, we found that SCD1 activity was strongly reduced at early (sub-clinical) disease stage, and that this reduction could explain in itself the alteration of lipid metabolism characteristic of ALS. The impact of loss of SCD1 activity for the motor axis was then studied. Genetic deletion or pharmacological inhibition of SCD1 enhanced functional recovery after sciatic nerve injury in mice. Wefurther explored if the loss of SCD1 activity found in SOD1 mice is a protective mechanism elicited in response to ALS. We treated SOD1 mice with an inhibitor of SCD1 activity. The treatment resulted in exacerbated muscular oxidative metabolism,preservation of neuromuscular integrity and enhanced motor neuron survival. We conclude that inhibition of SCD1 represents a promising therapeutic target for ALS
Dalle, Heloïse. "Rôle du récepteur adipocytaire des glucocorticoïdes dans les troubles métaboliques liés à un traitement par la corticostérone Adipocyte glucocorticoid receptor deficiency promotes adipose tissue expandability and improves the metabolic profile under corticosterone exposure Glucocorticoid-induced insulin resistance is related to macrophage visceral adipose tissue infiltration." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS065.pdf.
Glucocorticoids (GC) are among the medications most commonly prescribed because of their anti-inflammatory and immunosuppressive properties. However, high doses can lead to side effects including GC-induced diabetes and lipodystrophy. The contribution of adipocyte glucocorticoid receptor (GR) in the molecular mechanisms of these complications remains to be investigated. The goal of this study was to determine the precise role of the GR in the development of insulin-resistance and associated metabolic dysregulations in a context of hypercorticism. For this purpose, we have generated an inducible mouse model of GR invalidation specifically in the adipocyte (AdipoGR-KO), which was submitted to a four-week corticosterone treatment. Metabolic phenotype of AdipoGR-KO mice showed an increase of fat mass associated with a paradoxical improvement of glucose tolerance, insulin sensitivity, lipid profile and liver steatosis compared to WT mice. Preferential and beneficial fat storage in adipose tissue prompted us to investigate the mechanisms involved in the excessive development of adipose tissue, in particular the vascularization. Surprisingly, our results showed a higher development of capillary network in fat pads of AdipoGR-KO mice, associated with a strong induction of the angiogenic factor VEGF-A and its transcriptional regulator HIF-1α. Thus, we show for the first time that GR could be a limiting factor of adipose tissue expansion through the inhibition of the angiogenic process