Thesis (Ph. D.)--University of Oklahoma. / Includes bibliographical references.

L'obésité est un problème de santé mondial et grandissant qu'on qualifie d'épidémie. Les problèmes de santé associés au stress sont aussi en croissance. Ces deux phénomènes découlent de nouvelles habitudes de vie. Les travaux de cette thèse visaient à caractériser davantage le lien entre le stress et l'obésité. Premièrement, nous avons tenté d'élargir les connaissances au sujet de l'influence de l'obésité, mais aussi de la perte de poids, sur la réactivité de l'axe hypothalamo-hypophysosurrénalien (HHS), chez des hommes à distribution centrale et des femmes à distribution périphérique du tissu adipeux. La réponse à trois types de stimulations de l'axe HHS a été mesurée chez des individus minces, obèses et à obésité réduite: le test acoustique de sursaut, le test social de stress de Trier et la sécrétion de cortisol en réponse au réveil (SCR). Le test acoustique de sursaut n'a révélé aucune différence marquée entre les différents groupes alors que les deux autres stimulations de l'axe HHS se sont avérées complémentaires. Globalement, les résultats obtenus confirment une hyperréactivité de l'axe HHS dans l'état d'obésité abdominale chez les hommes, alors qu'après une perte de poids, la réactivité s'atténue. Chez les femmes, bien que l'accumulation de graisse périphérique ne semble pas modifier l'état de l'axe HHS, la perte de poids est associée à une réactivité accrue de celui-ci. Deuxièmement, nous avons voulu déterminer si ce lien entre le statut pondéral et l'axe corticotrope était associé aux comportements alimentaires et à la préoccupation à l'égard du poids corporel. Une série de questionnaires nous ont permis d'établir que la SCR chez les femmes est négativement associée à plusieurs des variables mesurées, la susceptibilité émotionnelle à la désinhibition alimentaire ressortant parmi celles-ci. Ainsi, malgré que nous soyons encore loin d'avoir fait toute la lumière sur le lien entre le stress et l'obésité, ces travaux nous ont permis de consolider des observations faites par d'autres groupes de recherche et de faire un pas en avant concernant la mesure de la SCR qui est non seulement reliée au statut pondéral, mais à des comportements qui influencent le poids corporel et l'état de stress des individus. / Obesity is a health problem reaching more and more people and is now considered as a world-wide epidemic. Stress-related health problems also increased during the last decades. The parallel evolution of these two phenomena is not that surprising, since they are both ensuing from our modem life habits. The work of this thesis consisted in better understanding the link between stress and obesity. First, we attempted to enlarge our knowledge about the influence of obesity, but also weight loss, on the hypothalamic-pituitary-adrenal (HPA) axis in men with central and women with peripheral body fat distribution. The response to three types of HPA axis stimulations was assessed in lean, obese and reduced obese subjects: the acoustic startle test (AST), the Trier social stress test and the awakening cortisol response (ACR). The AST revealed no marked difference between the three different weight status groups, while the two other HPA axis stimulations turned out complementary. Globally, the obtained results confirm a hyperreactivity of the HPA axis in abdominal obesity state in men, whereas the reactivity is attenuating with weight loss. In women, although peripheral fat accumulation does not seem to modify the HPA axis status, weight loss is associated with a heightened reactivity of the latter. Secondly, we tried to determine if this link between weight status and HPA axis was related to eating behavior and preoccupation towards body weight. A set of questionnaires permitted us to observe that ACR in women is negatively associated with many of the measured variables; and emotional susceptibility to disinhibition was the most relevant among them. Thus, despite the fact that we are still far to get right from the bottom of the link between stress and obesity, this work allowed us to strengthen the observations made by other research groups and to make a great leap forward concerning the ACR, that revealed a measure related not only to weight status, but also to eating behavior influencing body weight and psychological stress state of individuals.

Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

Pup directed maternal licking and grooming (LG) increases with corticosterone (CORT) supplimentation (Rees et al 2004). Increases in LG lead to an attenuation of the adult offspring's HPA response to stress (Liu et aI1997). Similarly, Neonatal increases in glucocorticoids lead, in adulthood, to the same attenuation of the HPA stress response (Catalani et aI1993). We hypothesize that dams exhibiting increased LG will have increased circulating CORT, and this increase will be reflected in their offspring. This thesis characterizes the HPA hormone profile adrenocorticotropic hormone (ACTH), CORT & Corticosterone Binding Globulin (CBG) in High LG (H) and Low LG (L) litters, 5 days postpartum (P4). Furthermore pup plasma CORT levels are determined at (P) 3,4,6,10 & 14. Finally P10 Hand L LG ACTH, CORT & CBG will be assessed after stress. RESULTS: H compared to L LG dams have significantly increased plasma CORT (p=0.03). At P4, H LG offspring have significantly increased plasma CORT (p=0.03) and significantly decreased plasma ACTH (p=0.04) as compared to L LG offspring. Plasma CBG levels are significantly lower in H compared to L LG offspring (p=0.01) at the same age. Across the Stress Hyporesponsive Period (SHRP) H LG offspring had significantly increased plasma CORT (p= 0.00) compared to L LG offspring at P3. Challenged with a stressor at P10, H LG offspring have an exaggerated plasma CORT response (p=0.00). This data suggests increases in plasma CORT in the dams leads to increased CORT in the high offspring, contributing perhaps to a more mature stress response at P10. / Key word abbreviation: (1) CORT - CORTicosterone, (2) ACTH - AdrenoCorticoTropin releasing Hormone, (3) CBG - Corticosteroid Binding Globulin, (4) SHRP - Stress Hypo-Responsive Period, (5) P - Post-natal day, (6) HPA - Hypothalamic-Pituitary-Adrenal, (7) LG - Licking/Grooming, (8) ADX/OVX - ADrenalectomized/OVarectomized.

The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

No description available.

No description available.

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2008-2009 / Les troubles alimentaires sont sérieux et peuvent mettre la vie de ceux qui en souffrent en danger. Une activité anormale de Taxe hypothalamo-hypophyso-surrénalien et une dysfonction de l'hypothalamus sont d'ailleurs associées aux troubles alimentaires. En outre, les récents rapports cliniques soulignent le rôle du thalamus dans les troubles alimentaires puisqu'une lésion du thalamus dorsal, particulièrement le noyau paraventriculaire thalamique (PVT), affecte sévèrement la sensibilité des patients au stress de même que leur alimentation. Les projections réciproques du PVT à l'hypothalamus, au système limbique et au cortex préfrontal suggèrent que cette région est en bonne position pour moduler le comportement alimentaire et l'activité de l'axe hypothalamo-hypophyso-surrénalien. Ce projet visait à étudier la localisation de l'oscillateur entraîné par la prise alimentaire (FEO) en caractérisant la dynamique de l'activation neuronale dans le cerveau des rats pendant l'anticipation alimentaire et suite à la prise alimentaire et d'étudier la régulation de l'activité de l'axe HPA en fonction de la condition alimentaire. Les résultats obtenus suggèrent que le FEO pourrait être représenté par un réseau neuronal distribué, le circuit septohippocampal-thalamo-hypothalamique. Les subdivisions du PVT et de plusieurs noyaux hypothalamiques ont d'ailleurs des rôles différents en fonction de la condition alimentaire. De plus, les résultats obtenus démontrent que la dynamique de l'activation neuronale de l'anticipation alimentaire est différente de celle de la prise alimentaire. Finalement, les résultats ont montré que l'activation de l'axe hypothalamo-hypophyso-surrénalien au niveau périphérique n'est pas accompagnée de l'activation des neurones à corticolibérine. Ce projet a permis d'acquérir des connaissances détaillées sur la neuroanatomie et la neurophysiologie du thalamus et de l'hypothalamus impliqués dans la régulation de la prise alimentaire. En outre, ce projet a aidé à mieux comprendre les mécanismes centraux liés à l'augmentation de la prise alimentaire et à l'obésité, la pathologie considérée actuellement par l'Organisation Mondiale de la Santé comme une maladie de dimension pandémique.

Les comportements motivés dont l‟addiction aux drogues d‟abus, mettent en jeu le système dopaminergique mésolimbique. Aussi connu sous le nom de système de la récompense, celui-ci comprend les neurones à dopamine de l‟aire tegmentale ventrale qui projettent, entre autres, vers le noyau accumbens. Tout comme les neurones de l‟hypothalamus, les neurones à dopamine de l‟aire tegmentale ventrale répondent aux hormones telles que la leptine, l‟insuline et la ghréline pour modifier la prise alimentaire, la motivation ou encore le tonus dopaminergique. Ceci indique que le système dopaminergique mésolimbique est sensible aux signaux hormonaux circulants et suggère que les neurones de l‟aire tegmentale ventrale pourraient percevoir les signaux métaboliques comme le glucose ou les acides gras. De plus, plusieurs études chez les humains et les rongeurs démontrent que l‟obésité et les diètes riches en gras affectent négativement la fonction dopaminergique mésolimbique. Étant donné les lacunes qui demeurent quant aux mécanismes impliqués dans la dysfonction du système dopaminergique mésolimbique induite par la nourriture riche en gras, nous avons cherché à évaluer les effets de l‟acide oléique et de l‟acide palmitique, deux des acides gras les plus abondants dans l‟organisme et l‟alimentation contemporaine, sur le système de la récompense. Ces deux acides gras, l‟un saturé (acide palmitique) et l‟autre mono-insaturé (acide oléique), se distinguent par leurs effets différentiels sur la prise alimentaire, la signalisation hormonale ou encore leur métabolisme intracellulaire mais aussi sur la santé cardiovasculaire et mentale. Nous avons dans un premier temps évalué la capacité du système dopaminergique mésolimbique à détecter les acides gras. Nous avons comparé les effets de l‟injection d‟acide oléique ou d‟acide palmitique dans l‟aire tegmentale ventrale sur la prise alimentaire, la motivation et l‟activité électrique des neurones à dopamine de l‟aire tegmentale ventrale. Nos résultats montrent que l‟acide oléique, mais pas l‟acide palmitique, diminue la prise alimentaire et le comportement motivé. L‟acide oléique inhibe également l‟activité électrique des neurones à dopamine, ces effets semblent dépendre de son entrée dans la cellule. De plus, nous montrons que les neurones à dopamine de l‟aire tegmentale ventrale expriment plusieurs 3 gènes de protéines importantes pour le transport et le métabolisme des acides gras et qu‟ils sont capables de d‟incorporer les acides gras. Nous avons dans un second temps évalué les effets de l‟acide oléique et de l‟acide palmitique dérivés de l‟alimentation. Nous avons soumis des rats à l‟une de ces trois diètes : une riche en gras enrichie en acide oléique, une riche en gras enrichie en acide palmitique ou une contrôle faible en gras. Après huit semaines, et en l‟absence d‟obésité ou d‟altérations métaboliques majeures, la diète enrichie en acide palmitique, mais pas la diète isocalorique enrichie en acide oléique, induit une hyposensibilité aux effets récompensants et locomoteurs de l‟amphétamine, associée, entre autres, à la diminution de la signalisation du récepteur à la dopamine D1R et de l‟expression du transporteur de la dopamine. Nous avons finalement exploré l‟impact de ces diètes sur l‟activité de l‟axe hypothalamo-hypophysaire-surrénalien. Les résultats montrent que la diète enrichie en acide palmitique altère aussi la fonction de l‟axe et l‟expression de plusieurs gènes cibles des corticostéroïdes, sans toutefois modifier le comportement anxieux. Ce travail de doctorat vient compléter les connaissances sur les dysfonctions du système dopaminergique mésolimbique induites par la nourriture riche en gras. Il met en lumière les effets différentiels des classes d‟acides gras et les mécanismes par lesquels ils modulent les comportements motivés et alimentaires. De façon chronique, avant l‟apparition d‟obésité et d‟altérations métaboliques, les acides gras saturés, et non les acides gras mono-insaturés, issus de l‟alimentation perturbent le fonctionnement de l‟axe hypothalamo-hypophysaire-surrénalien et réduisent la fonction dopaminergique. Ceci pourrait contribuer à perpétuer la recherche et la prise de ce type d‟acides gras afin de compenser ce déficit. / The mesolimbic dopamine system, also known as the reward system, is well recognized for its role in motivated reward-related behaviours such as drug addiction. It consists of dopamine neurons originating in the ventral tegmental area that project, among others, to the nucleus accumbens. Similar to neurons in the hypothalamus, dopamine neurons in the ventral tegmental area can detect circulating hormones such as leptin, insulin and ghrelin to adjust food intake, motivation and dopamine tone. This suggests that they could also perceive nutritional signals like glucose and fatty acids. Moreover, several lines of evidence exist showing that palatable food enriched in fat and obesity reduce mesolimbic dopamine function. Given the many unknowns regarding the mechanisms of obesity-induced dopamine dysfunction, and given that fatty acids differentially influence cardiovascular and mental health according to their class, we sought to determine the effects of the monounsaturated fatty acid oleic acid and the saturated fatty acid palmitic acid, two of the most abundant fatty acids in the body and foods, on mesolimbic dopamine function. Notably palmitic acid and oleic acid differ in their intracellular metabolic fate as well as in their effects on food intake and leptin and insulin signaling at the level of the hypothalamus. We first evaluated the fatty acid sensing properties of the mesolimbic dopamine system. We looked at the effects of the injection of oleic acid or palmitic acid in the ventral tegmental area on food intake, motivation and dopamine neurons activity. Our results demonstrate that oleic acid, but not palmitic acid, reduces basal and motivated feeding behavior and neuronal activity. Those effects seem to be dependent on its entry into the cell. Moreover, using a neurons culture system we show that dopamine neurons can uptake fatty acids. We then examined the effect of food-derived oleic and palmitic acid on mesolimbic dopamine function. We assigned rats to a low-fat control diet or to one or the other of a high-fat diet: one enriched in oleic acid or one enriched in palmitic acid. The two high-fat diets are isocaloric and differed only in the fat source. Following eight weeks of feeding, the palmitic 5 acid-enriched high-fat diet, but not the oleic acid-enriched diet, decreased the sensitivity to the rewarding and locomotor-sensitizing effects of amphetamine. This was associated with a reduction of dopamine receptor D1R signaling and dopamine transporter expression. Importantly this occured independently of weight gain and hormonal changes. Lastly, we explored the impact of those diets on the activity of the hypothalamus-pituitary-adrenal axis. Results show that the saturated fat diet alters the function of the axis as well as the expression of several keys genes targeted by glucocorticoids in the hypothalamus but without affecting anxiety-related behavior. This work provides further insight into how the mesolimbic dopamine system is altered by high-fat food consumption. It brings light to the differential effects of two classes of fatty acids and the mechanisms by which they modulate food intake and motivation. The prolonged intake of saturated fat, but not mono-unsaturated fat, disrupts the hypothalamus-pituitary-adrenal axis and decreases mesolimbic dopamine function prior to the onset of obesity and major metabolic alterations. Dysfunction of dopaminergic systems induced by saturated fat consumption could promote further intake of such palatable food as a means to compensate for reward hyposensitivity.