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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Serotonin neurons maintain central mechanisms regulating metabolic homeostasis and are vital to thermogenic activation

McGlashon, Jacob 01 January 2016 (has links)
Thermogenic brown and beige adipocytes convert chemical energy to heat by metabolizing glucose and lipids via uncoupling protein 1 (Ucp1), a process known as non-shivering thermogenesis. Serotonin (5-HT) neurons in the ventral medulla are known to regulate sympathetic efferent neurons in the intermediolateral nucleus (IML) necessary to maintain brown adipose tissue (BAT) activity. Previous studies show that mice lacking central 5-HT neurons are incapable of maintaining body temperature in cold, ambient conditions. Due to this direct linkage between 5-HT and thermoregulation, we hypothesized that central 5-HT neurons may be vital to the regulation of brown and beige adipocyte activity. Given that BAT consumes large amounts of substrate when active, we also hypothesized that inactivation of BAT due to deletion of the regulatory neural circuitry (5-HT neurons) would cause metabolic dysregulation. To test this, we generated mice in which the human diphtheria toxin (DT) receptor was selectively expressed in central 5-HT neurons under control of a Pet-1 promoter. Pet-1 is a transcription factor selectively located in mature, central 5-HT neurons. Coincidentally, some cells within pancreatic islets also express Pet-1, and contain adequate machinery to produce, release, and uptake 5-HT. Systemic treatment with DT eliminated 5-HT neurons and caused loss of thermoregulation, BAT steatosis, and a >50% decrease in Ucp1 expression in BAT and beige fat, indicative of reduced thermal production. In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold and triglycerides 6.5-fold. Intracerebroventricular (ICV) treatment with 1/30th the systemic dose of DT induced an even greater thermoregulatory impairment. The metabolic deficits following systemic DT treatment indicate that central 5-HT neurons are essential for proper metabolic regulation. However, such high levels of glucose and lipids also indicate failure of the pancreatic endocrine program following systemic treatment, likely due to moderate destruction of β-cells expressing Pet-1 and the DT receptor. Because ICV treatment caused even greater thermoregulatory and metabolic deficits, where little, if any, of the toxin would spread systemically, central 5-HT neurons are clearly essential for normal central regulation of metabolism. Interestingly, similar BAT and beige fat defects occurred in Lmx1bf/f/p mice, in which 5-HT neurons fail to develop in utero. Assessment of systemically treated animals using a euglycemic/hyperinsulinemic clamp showed extensive fasting hyperglycemia and systemic insulin resistance, coinciding with reduced glucose uptake in skeletal muscle and BAT. The hyperinsulinemic clamp failed to suppress hepatic glucose and fatty acid production, leading to the conclusion that loss of central 5-HT neurons disrupts central hepatic regulation. In attempts to induce BAT thermogenesis and metabolism, we optogenetically stimulated 5-HT neurons in the rostral raphe pallidus and measured BAT and body temperature along with blood glucose. Unfortunately, these stimulations were incapable of increasing BAT temperature and lowering blood glucose, perhaps limiting therapeutic potential of these 5-HT neurons. We conclude that 5-HT neurons are major players in central regulation of metabolic homeostasis, in part through recruitment and activation of brown and beige adipocytes and hepatic substrate production. Data also suggest that 5-HT neurons regulate glucose homeostasis via undefined neural mechanisms independently of BAT activity and pancreatic insulin secretion. Cumulative data on central 5-HT neurons indicate they are master regulators of whole-body metabolism.
12

Control of Uncoupling Protein-1 (UCP1) by Phosphorylation and the Metabolic Impact of Ectopic UCP1 Expression in Skeletal Muscle of Mice

Adjeitey, Cyril 07 June 2013 (has links)
UCP1 is a member of the mitochondrial transmembrane anion carrier protein superfamily and is required to mediate adaptive thermogenesis in brown adipose tissue (BAT). Once activated, UCP1 uncouples mitochondrial respiration from ATP synthesis, thereby wasting the protonmotive force formed across the mitochondrial inner membrane as heat. It is hypothesized that proton leaks through UCP1 could be a molecular target to combat certain forms of obesity. Although it is well established that UCP1 is regulated by allosteric mechanisms, alternative methods such as post-translational modification still remain to be explored. The aims of the present study were to confirm the phosphorylation of UCP1 and the physiological relevance of this modification. Using isoelectric focusing, we confirmed that UCP1 displayed acidic shifts consistent with phosphorylation in BAT mitochondria isolated from cold exposed versus warm acclimated mice. A mouse model that ectopically expressed UCP1 in skeletal muscle was used to explore the link between the mitochondrial redox status and UCP1 function. Our results show that the expression of UCP1 in skeletal muscle led to decreases in body and tissues weights. In contrast, glucose uptake into skeletal muscle, food intake and energy expenditure was increased with the expression of UCP1. Finally, proton leaks through UCP1 were determined to be increased in isolated mitochondria from transgenic versus wild-type mice. Taken together these results indicate a complex interplay between mitochondrial redox status, post-translational modification and UCP1 function. Elucidation of novel mechanisms regulating UCP1 offers alternatives strategies that can be explored in order to modulate BAT thermogenesis.
13

Vztah úspěšnosti redukční terapie dětské obezity k vybraným genetickým polymorfizmům. / Relation of fruitfulness in reduction therapy of child obesity at samplet genetics polymophisms

Janoudová, Veronika January 2011 (has links)
The aim of the thesis is to analyze the relationship of polymorphisms Ala54Thr FABP2 (protein binding long chain fatty acids in the enterocytes of the small intestine), Gln27Glu B2AR (lipolytic receptor in white adipose tissue) and A-3826G UCP1 (uncoupling protein in the inner membrane of mitochondria in brown adipose tissue) to pursued antropometric and biochemical markers and judge their impact on the success of reducing therapy on children. Association of observed polymorphisms with obesity has already been proven in other studies, the results are inconsistent and most studies have dealt with adults. The study includes of 335 individuals (216 girls and 119 boys) who completed a reduction stay in the Children's hospital of Dr. Filip in Poděbrady. The subjects were studied for anthropometric and biochemical markers at the beginning and at the end of reduction stay. Genetic analysis of polymorphisms were performed with use of PCR-RFLP. Girls Thr/Thr in polymorphism Ala54Thr FABP2 were showing greater thickness of skin fold on abdomen (p=0,009) and higher fat percentage in body composition (p=0,023). Significantly greater reductionof both these markers have been demonstrated (p=0.008, p=0.040). For boys the relationship was observed of homozygote Ala/Ala in a lower weight reduction (p=0,040). In...
14

Control of Uncoupling Protein-1 (UCP1) by Phosphorylation and the Metabolic Impact of Ectopic UCP1 Expression in Skeletal Muscle of Mice

Adjeitey, Cyril January 2013 (has links)
UCP1 is a member of the mitochondrial transmembrane anion carrier protein superfamily and is required to mediate adaptive thermogenesis in brown adipose tissue (BAT). Once activated, UCP1 uncouples mitochondrial respiration from ATP synthesis, thereby wasting the protonmotive force formed across the mitochondrial inner membrane as heat. It is hypothesized that proton leaks through UCP1 could be a molecular target to combat certain forms of obesity. Although it is well established that UCP1 is regulated by allosteric mechanisms, alternative methods such as post-translational modification still remain to be explored. The aims of the present study were to confirm the phosphorylation of UCP1 and the physiological relevance of this modification. Using isoelectric focusing, we confirmed that UCP1 displayed acidic shifts consistent with phosphorylation in BAT mitochondria isolated from cold exposed versus warm acclimated mice. A mouse model that ectopically expressed UCP1 in skeletal muscle was used to explore the link between the mitochondrial redox status and UCP1 function. Our results show that the expression of UCP1 in skeletal muscle led to decreases in body and tissues weights. In contrast, glucose uptake into skeletal muscle, food intake and energy expenditure was increased with the expression of UCP1. Finally, proton leaks through UCP1 were determined to be increased in isolated mitochondria from transgenic versus wild-type mice. Taken together these results indicate a complex interplay between mitochondrial redox status, post-translational modification and UCP1 function. Elucidation of novel mechanisms regulating UCP1 offers alternatives strategies that can be explored in order to modulate BAT thermogenesis.
15

Critical roles of nardilysin in the maintenance of body temperature homoeostasis / ナルディライジンは体温恒常性維持に重要な役割を果たす

Matsuoka, Tatsuhiko 23 May 2014 (has links)
Yoshinori Hiraoka, Tatsuhiko Matsuoka, Mikiko Ohno, Kazuhiro Nakamura, Sayaka Saijo, Shigenobu Matsumura, Kiyoto Nishi, Jiro Sakamoto, Po-Min Chen, Kazuo Inoue, Tohru Fushiki, Toru Kita, Takeshi Kimura & Eiichiro Nishi "Critical roles of nardilysin in the maintenance of body temperature homoeostasis" Nature Communications 5, Article number: 3224 doi:10.1038/ncomms4224 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18454号 / 医博第3909号 / 新制||医||1004(附属図書館) / 31332 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 福田 和彦, 教授 瀬原 淳子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
16

Analysis of gene expression associated with drug-induced hyperthermia in rat

Pachhain, Sudhan 07 August 2019 (has links)
No description available.
17

Impact de la citrulline sur le métabolisme du tissu adipeux / Citrulline effect on adipose tissue metabolism

Joffin, Nolwenn 29 January 2015 (has links)
L’obésité s’accompagne de pathologies comme le diabète de type 2 et les maladies cardiovasculaires, liées à des dérégulations métaboliques et endocriniennes du tissu adipeux blanc (TAB). Au cours du vieillissement, la perte de masse musculaire peut être associée à l’obésité et définit le concept d’obésité sarcopénique. Les traitements mis en œuvre pour contrecarrer ces pathologies n’ont qu’un succès très partiel. Il est donc opportun de développer des stratégies alternatives originales qui pourraient aboutir à des thérapeutiques ciblées. Notre équipe étudie les régulations métaboliques du TAB, source majeure de stockage de l’énergie de l’organisme. Les triglycérides stockés sont libérés à jeun grâce à la lipolyse qui libère les acides gras non-estérifiés (AGNE) et le glycérol dans le sang, comme source d’énergie des autres tissus. En plus de la β-oxydation des AGNE, leur ré-estérification partielle intervient pour limiter leur libération lors de la lipolyse. La glycéronéogenèse est nécessaire à la ré-estérification en situation de jeûne. Des études préalables ont montré que l'administration de citrulline (CIT) pendant trois mois à des rats vieillissants induit une diminution d’environ 40% de la masse viscérale du TAB. Cet acide aminé non protéique est un complément alimentaire donné au cours du vieillissement ou à des sportifs pour augmenter la masse musculaire. Nous avons étudié les effets de la CIT sur des cultures d’explants de TAB de rats. Dans la première partie de ce travail, nous montrons que la CIT a un effet direct lipolytique et anti-glycéronéogénique sur les explants des rats qu’ils soient jeunes ou âgés. Cependant, la libération des AGNE du TAB des rats jeunes est limitée par une augmentation de la capacité oxydative du tissu. Avec l’âge, la masse du TAB augmente en parallèle à l’augmentation d’un état pro-inflammatoire. Afin de comprendre l’influence de ces deux paramètres indépendamment de l’âge, nous avons étudié dans la deuxième partie de ce travail, les effets de la CIT sur les explants de TAB de rats jeunes soumis à un régime contrôle (CD) ou hyperlipidique (HFD). Nous observons une augmentation, induite par la CIT, de la lipolyse et de la capacité ß-oxydative du TAB des rats quel que soit le régime, alors que la glycéronéogenèse est diminuée. Toutefois, les AGNE sont sélectivement libérés par le TAB de rats HFD, en relation avec une réduction drastique de leur ré-estérification. Le NO est un médiateur de ces effets. Dans une troisième partie, nous démontrons que la CIT agit directement sur le TAB de rats CD et HFD pour induire l'expression de la protéine découplante, UCP1, en lien avec le « brunissement » potentiel du TAB par cet acide aminé. Ces effets ne sont pas observés au sein du TAB des rats âgés. L’ensemble de nos résultats établit les bases pour de futures investigations visant à élucider les mécanismes par lesquels la CIT réduit la masse adipeuse et ouvre de nouvelles perspectives thérapeutiques pour lutter contre le surpoids et l’obésité sarcopénique. / Obesity is frequently associated with type 2 diabetes and cardiovascular diseases, related to metabolic and endocrine dysregulation of white adipose tissue (WAT). During aging, the loss of muscle mass may be associated with obesity and defines the concept of sarcopenic obesity. Treatments implemented to counteract these conditions showed a very partial success. It is therefore appropriate to develop original alternative strategies that could lead to targeted therapies. Our team studies the metabolic regulation of WAT, the major source of energy storage in the body. Non-esterified fatty acids (NEFA) and glycerol are released in the blood from stored triglycerides through lipolysis and used as a source of energy for other tissues. In addition to their β-oxidation, NEFA are re-esterified in part, a process that limits their release in the blood. Glyceroneogenesis is the pathway necessary to NEFA re-esterification in the fasting state. Previous studies showed that administration of citrulline (CIT) for three months to aging rats induced a decrease of approximately 40% of the visceral WAT mass. This non-protein amino acid is given as a dietary supplement during aging or sports to increase muscle mass. We studied the effects of CIT on explant cultures of rat WAT. In the first part of this work, we show that CIT exerts a direct lipolytic and anti-glyceroneogenic effect on explants from rats whether young or old. However, the release of NEFA from the explants of young rats is limited by an increase in the oxidative capacity of the tissue. During aging, WAT mass augments in parallel to the increase in a pro-inflammatory state. To understand the influence of these two parameters regardless of age, we studied in the second part of this work, the effects of CIT on WAT explants from young rats fed a control (CD) or high fat (HFD) diet. We show an CIT-induced increase in lipolysis and beta-oxidative capacity of WAT from rats whatever the diet, while glyceroneogenesis is reduced. However, NEFA are selectively released from WAT of HFD rats, in connection with a drastic reduction of their re-esterification. NO is a mediator of these effects. In the third part of this work, we show that CIT acts directly on WAT from CD and HFD rats to induce the expression of uncoupling protein, UCP1, in line with the potential "browning" of WAT by this amino acid. These effects were not observed in explants from old rats. Altogether our results establish the basis for future investigations aimed at elucidating the mechanisms by which CIT reduces body fat and open new therapeutic perspectives to fight overweight and sarcopenic obesity.
18

Impact de la citrulline sur le métabolisme du tissu adipeux / Citrulline effect on adipose tissue metabolism

Joffin, Nolwenn 29 January 2015 (has links)
L’obésité s’accompagne de pathologies comme le diabète de type 2 et les maladies cardiovasculaires, liées à des dérégulations métaboliques et endocriniennes du tissu adipeux blanc (TAB). Au cours du vieillissement, la perte de masse musculaire peut être associée à l’obésité et définit le concept d’obésité sarcopénique. Les traitements mis en œuvre pour contrecarrer ces pathologies n’ont qu’un succès très partiel. Il est donc opportun de développer des stratégies alternatives originales qui pourraient aboutir à des thérapeutiques ciblées. Notre équipe étudie les régulations métaboliques du TAB, source majeure de stockage de l’énergie de l’organisme. Les triglycérides stockés sont libérés à jeun grâce à la lipolyse qui libère les acides gras non-estérifiés (AGNE) et le glycérol dans le sang, comme source d’énergie des autres tissus. En plus de la β-oxydation des AGNE, leur ré-estérification partielle intervient pour limiter leur libération lors de la lipolyse. La glycéronéogenèse est nécessaire à la ré-estérification en situation de jeûne. Des études préalables ont montré que l'administration de citrulline (CIT) pendant trois mois à des rats vieillissants induit une diminution d’environ 40% de la masse viscérale du TAB. Cet acide aminé non protéique est un complément alimentaire donné au cours du vieillissement ou à des sportifs pour augmenter la masse musculaire. Nous avons étudié les effets de la CIT sur des cultures d’explants de TAB de rats. Dans la première partie de ce travail, nous montrons que la CIT a un effet direct lipolytique et anti-glycéronéogénique sur les explants des rats qu’ils soient jeunes ou âgés. Cependant, la libération des AGNE du TAB des rats jeunes est limitée par une augmentation de la capacité oxydative du tissu. Avec l’âge, la masse du TAB augmente en parallèle à l’augmentation d’un état pro-inflammatoire. Afin de comprendre l’influence de ces deux paramètres indépendamment de l’âge, nous avons étudié dans la deuxième partie de ce travail, les effets de la CIT sur les explants de TAB de rats jeunes soumis à un régime contrôle (CD) ou hyperlipidique (HFD). Nous observons une augmentation, induite par la CIT, de la lipolyse et de la capacité ß-oxydative du TAB des rats quel que soit le régime, alors que la glycéronéogenèse est diminuée. Toutefois, les AGNE sont sélectivement libérés par le TAB de rats HFD, en relation avec une réduction drastique de leur ré-estérification. Le NO est un médiateur de ces effets. Dans une troisième partie, nous démontrons que la CIT agit directement sur le TAB de rats CD et HFD pour induire l'expression de la protéine découplante, UCP1, en lien avec le « brunissement » potentiel du TAB par cet acide aminé. Ces effets ne sont pas observés au sein du TAB des rats âgés. L’ensemble de nos résultats établit les bases pour de futures investigations visant à élucider les mécanismes par lesquels la CIT réduit la masse adipeuse et ouvre de nouvelles perspectives thérapeutiques pour lutter contre le surpoids et l’obésité sarcopénique. / Obesity is frequently associated with type 2 diabetes and cardiovascular diseases, related to metabolic and endocrine dysregulation of white adipose tissue (WAT). During aging, the loss of muscle mass may be associated with obesity and defines the concept of sarcopenic obesity. Treatments implemented to counteract these conditions showed a very partial success. It is therefore appropriate to develop original alternative strategies that could lead to targeted therapies. Our team studies the metabolic regulation of WAT, the major source of energy storage in the body. Non-esterified fatty acids (NEFA) and glycerol are released in the blood from stored triglycerides through lipolysis and used as a source of energy for other tissues. In addition to their β-oxidation, NEFA are re-esterified in part, a process that limits their release in the blood. Glyceroneogenesis is the pathway necessary to NEFA re-esterification in the fasting state. Previous studies showed that administration of citrulline (CIT) for three months to aging rats induced a decrease of approximately 40% of the visceral WAT mass. This non-protein amino acid is given as a dietary supplement during aging or sports to increase muscle mass. We studied the effects of CIT on explant cultures of rat WAT. In the first part of this work, we show that CIT exerts a direct lipolytic and anti-glyceroneogenic effect on explants from rats whether young or old. However, the release of NEFA from the explants of young rats is limited by an increase in the oxidative capacity of the tissue. During aging, WAT mass augments in parallel to the increase in a pro-inflammatory state. To understand the influence of these two parameters regardless of age, we studied in the second part of this work, the effects of CIT on WAT explants from young rats fed a control (CD) or high fat (HFD) diet. We show an CIT-induced increase in lipolysis and beta-oxidative capacity of WAT from rats whatever the diet, while glyceroneogenesis is reduced. However, NEFA are selectively released from WAT of HFD rats, in connection with a drastic reduction of their re-esterification. NO is a mediator of these effects. In the third part of this work, we show that CIT acts directly on WAT from CD and HFD rats to induce the expression of uncoupling protein, UCP1, in line with the potential "browning" of WAT by this amino acid. These effects were not observed in explants from old rats. Altogether our results establish the basis for future investigations aimed at elucidating the mechanisms by which CIT reduces body fat and open new therapeutic perspectives to fight overweight and sarcopenic obesity.
19

Impact de la citrulline sur le métabolisme du tissu adipeux / Citrulline effect on adipose tissue metabolism

Joffin, Nolwenn 29 January 2015 (has links)
L’obésité s’accompagne de pathologies comme le diabète de type 2 et les maladies cardiovasculaires, liées à des dérégulations métaboliques et endocriniennes du tissu adipeux blanc (TAB). Au cours du vieillissement, la perte de masse musculaire peut être associée à l’obésité et définit le concept d’obésité sarcopénique. Les traitements mis en œuvre pour contrecarrer ces pathologies n’ont qu’un succès très partiel. Il est donc opportun de développer des stratégies alternatives originales qui pourraient aboutir à des thérapeutiques ciblées. Notre équipe étudie les régulations métaboliques du TAB, source majeure de stockage de l’énergie de l’organisme. Les triglycérides stockés sont libérés à jeun grâce à la lipolyse qui libère les acides gras non-estérifiés (AGNE) et le glycérol dans le sang, comme source d’énergie des autres tissus. En plus de la β-oxydation des AGNE, leur ré-estérification partielle intervient pour limiter leur libération lors de la lipolyse. La glycéronéogenèse est nécessaire à la ré-estérification en situation de jeûne. Des études préalables ont montré que l'administration de citrulline (CIT) pendant trois mois à des rats vieillissants induit une diminution d’environ 40% de la masse viscérale du TAB. Cet acide aminé non protéique est un complément alimentaire donné au cours du vieillissement ou à des sportifs pour augmenter la masse musculaire. Nous avons étudié les effets de la CIT sur des cultures d’explants de TAB de rats. Dans la première partie de ce travail, nous montrons que la CIT a un effet direct lipolytique et anti-glycéronéogénique sur les explants des rats qu’ils soient jeunes ou âgés. Cependant, la libération des AGNE du TAB des rats jeunes est limitée par une augmentation de la capacité oxydative du tissu. Avec l’âge, la masse du TAB augmente en parallèle à l’augmentation d’un état pro-inflammatoire. Afin de comprendre l’influence de ces deux paramètres indépendamment de l’âge, nous avons étudié dans la deuxième partie de ce travail, les effets de la CIT sur les explants de TAB de rats jeunes soumis à un régime contrôle (CD) ou hyperlipidique (HFD). Nous observons une augmentation, induite par la CIT, de la lipolyse et de la capacité ß-oxydative du TAB des rats quel que soit le régime, alors que la glycéronéogenèse est diminuée. Toutefois, les AGNE sont sélectivement libérés par le TAB de rats HFD, en relation avec une réduction drastique de leur ré-estérification. Le NO est un médiateur de ces effets. Dans une troisième partie, nous démontrons que la CIT agit directement sur le TAB de rats CD et HFD pour induire l'expression de la protéine découplante, UCP1, en lien avec le « brunissement » potentiel du TAB par cet acide aminé. Ces effets ne sont pas observés au sein du TAB des rats âgés. L’ensemble de nos résultats établit les bases pour de futures investigations visant à élucider les mécanismes par lesquels la CIT réduit la masse adipeuse et ouvre de nouvelles perspectives thérapeutiques pour lutter contre le surpoids et l’obésité sarcopénique. / Obesity is frequently associated with type 2 diabetes and cardiovascular diseases, related to metabolic and endocrine dysregulation of white adipose tissue (WAT). During aging, the loss of muscle mass may be associated with obesity and defines the concept of sarcopenic obesity. Treatments implemented to counteract these conditions showed a very partial success. It is therefore appropriate to develop original alternative strategies that could lead to targeted therapies. Our team studies the metabolic regulation of WAT, the major source of energy storage in the body. Non-esterified fatty acids (NEFA) and glycerol are released in the blood from stored triglycerides through lipolysis and used as a source of energy for other tissues. In addition to their β-oxidation, NEFA are re-esterified in part, a process that limits their release in the blood. Glyceroneogenesis is the pathway necessary to NEFA re-esterification in the fasting state. Previous studies showed that administration of citrulline (CIT) for three months to aging rats induced a decrease of approximately 40% of the visceral WAT mass. This non-protein amino acid is given as a dietary supplement during aging or sports to increase muscle mass. We studied the effects of CIT on explant cultures of rat WAT. In the first part of this work, we show that CIT exerts a direct lipolytic and anti-glyceroneogenic effect on explants from rats whether young or old. However, the release of NEFA from the explants of young rats is limited by an increase in the oxidative capacity of the tissue. During aging, WAT mass augments in parallel to the increase in a pro-inflammatory state. To understand the influence of these two parameters regardless of age, we studied in the second part of this work, the effects of CIT on WAT explants from young rats fed a control (CD) or high fat (HFD) diet. We show an CIT-induced increase in lipolysis and beta-oxidative capacity of WAT from rats whatever the diet, while glyceroneogenesis is reduced. However, NEFA are selectively released from WAT of HFD rats, in connection with a drastic reduction of their re-esterification. NO is a mediator of these effects. In the third part of this work, we show that CIT acts directly on WAT from CD and HFD rats to induce the expression of uncoupling protein, UCP1, in line with the potential "browning" of WAT by this amino acid. These effects were not observed in explants from old rats. Altogether our results establish the basis for future investigations aimed at elucidating the mechanisms by which CIT reduces body fat and open new therapeutic perspectives to fight overweight and sarcopenic obesity.
20

Implications du stress oxydant et du découplage mitochondrial dans les compromis entre traits d'histoire de vie / At the crossroad of metabolism and ageing : mitochondrial proximal control of oxidants and ultimate modulation of life history trade-offs

Stier, Antoine 24 October 2013 (has links)
L’attention scientifique s’est récemment portée sur l’identification des mécanismes proximaux sous-tendant les compromis évolutifs;tels que les compromis existant entre croissance/reproduction et longévité. La production d’espèces réactives de l’oxygène (ROS )a été suggérée comme un candidat potentiel ,de par sa liaison étroite au métabolisme énergétique (sous-­produits du fonctionnement mitochondrial) et son caractère inévitable. Si la production de ROS excède le niveau des défenses antioxydantes, une situation de stress oxydant va en résulter et a été associé au vieillissement . Puisque la mitochondrie n’est pas uniquement la centrale énergétique de la cellule mais aussi le principal producteur de ROS, cette thèse s’est attachée à clarifier les relations entre métabolisme énergétique , fonctionnement mitochondrial et stress oxydant ; avec des études concernant l’impact d’activités coûteuses en énergie (croissance, reproduction, thermogénèse) sur l’équilibre de la balance oxydative. / In recent years, scientific attention has turned towards the identification of the mechanisms underlying the trade-­‐offs occurring between growth rate/reproductive investment and longevity. Amongst these mechanisms, the production of reactive oxygen species (ROS) appears to be a key factor due both to its universal and inevitable nature. ROS are by-­‐products of energy processing by the mitochondria. If ROS production exceeds the capacity of the various antioxidant systems, oxidative stress will occur, and the accumulation of oxidative damage over time is thought to be a potential cause of ageing. Since mitochondria are not only the powerhouse of animal cells but also the main producer of ROS, this PhD thesis aimed to clarify the relationships between mitochondrial uncoupling state (i.e. efficiency to produce ATP), energy metabolism and oxidative stress. I investigated the impact of energy-­‐demanding activities such as thermogenesis, reproduction and growth on oxidative homeostasis.

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