Le système endocannabinoïde est un acteur majeur de la régulation de la balance énergétique. Cependant, son rôle au niveau de l’hypothalamus, une région critique dans la régulation de la balance énergétique, reste méconnu. L’objectif général de ce travail de thèse a été de disséquer le rôle du récepteur aux cannabinoïdes de type 1 (CB1) exprimé par des populations neuronales hypothalamiques spécifiques dans la régulation de la balance énergétique et l’homéostasie du glucose en caractérisant trois nouvelles lignées de souris possédant une mutation conditionnelle de CB1. En régime standard, la délétion de CB1 dans l’hypothalamus induit une augmentation de la dépense énergétique et une baisse de prise de poids corporel sans modifier la prise alimentaire alors que la délétion de CB1 dans le noyau ventromédian de l’hypothalamus (VMN-CB1-KO) entraîne une baisse significative de masse grasse, une augmentation de l’oxydation des acides gras in vivo, une augmentation de l’activité du système nerveux sympathique (SNS) et un métabolisme du glucose périphérique amélioré. Enfin, la délétion de CB1 dans le noyau paraventriculaire de l’hypothalamus (PVN-CB1-KO) induit une baisse de poids sans modifier la prise alimentaire ni la composition corporelle. Lors de l’exposition à un régime riche en graisses, les souris VMN-CB1-KO prennent plus de poids et de masse grasse que les WT, tandis que les souris PVN-CB1-KO sont partiellement protégées de l’obésité alimentaire grâce à une dépense énergétique accrue.Ces résultats suggèrent que CB1 exprimé par différentes populations hypothalamiques joue un rôle différent dans la régulation de la balance énergétique, qui dépend aussi du régime alimentaire. / The endocannabinoid system is a major player in energy balance regulation. However, a complete understanding of its role within the hypothalamus, a region critically involved in energy balance regulation, is still missing. The general aim of this PhD work was to dissect the specific role of the cannabinoid type 1 receptor (CB1) expressed on different hypothalamic neuronal populations in energy balance regulation and glucose homeostasis by characterizing three new mouse mutant lines with a conditional deletion of CB1. On standard diet, CB1 deletion within the hypothalamus induced an increase in energy expenditure and a decrease in body weight gain without modifying food intake, while CB1 deletion within the ventromedial nucleus of the hypothalamus (VMN-CB1-KO) decreased fat mass, increased fatty acid oxidation in vivo and sympathetic nervous system (SNS) activity, and improved peripheral glucose metabolism. CB1 deletion within the paraventricular nucleus of the hypothalamus (PVN-CB1-KO) decreased body weight gain without affecting food intake or body composition. When exposed to a high-fat diet, VMN-CB1-KO mice gained significantly more weight and fat mass than their WT, while PVN-CB1-KO mice were partly protected from diet-induced obesity thanks to increased energy expenditure. These results overall suggest that CB1 expressed on different hypothalamic neuronal populations have distinct roles in energy balance regulation, which in turn also depend on the diet consumed.

Call number: LD2668 .T4 1986 N47 / Master of Science / Human Nutrition

No description available.

Thesis (MTech (Consumer Science: Food and Nutrition))--Cape Peninsula University of Technology, 2016. / Objective: To determine the association between the dietary fat knowledge and consumption of foods rich in fat among first-year students in self-catering residence at a university of technology, Cape Town, South Africa. Design: The two concepts – the dietary fat knowledge (represented by dietary fat food knowledge and dietary fat nutrition knowledge) and the consumption of foods rich in fat – were assessed separately. Two norm-referenced, valid and reliable knowledge tests and an intake screening questionnaire were used for the assessments (as subsidiary objectives), before the associations between the concepts were determined (main objective). The dietary fat food and nutrition knowledge as assessed was categorised in the range poor or below average, average and good or above average, and the consumption of foods rich in fat as high, quite high, the typical Western diet, approaching low or desirable. The Pearson‟s chi-square test was applied to these categorical findings to determine if associations (five percent significance) existed between the concepts. Results: The stratified sample included 225 first-year students. Nearly half (48.4%) of them achieved an average fat food knowledge score, while the majority (80.9%) achieved a poor fat nutrition knowledge score. More than half (52.5%) either followed a typical Western diet, a diet quite high in fat or high in fat. While no significant (p > 0.05) association was found between the students‟ dietary fat food knowledge and consumption of foods rich in fat, significant results were found in the association between the students‟ dietary fat nutrition knowledge and consumption of foods rich in fat (p < 0.05) and between their fat food knowledge and fat nutrition knowledge (p < 0.001). Conclusions: An inverse association was found between the students‟ dietary fat nutrition knowledge and fat consumption, a positive association between their dietary fat food knowledge and dietary fat nutrition knowledge, and no association between their dietary fat food knowledge and fat consumption.

Este trabalho avaliou o efeito da dieta hiperlipídica em camundongos para o estudo da inflamação cardiovascular. Camundongos C57Bl/6 machos com 8 semanas de vida foram utilizados nos ensaios, sendo divididos nos grupos dieta controle e dieta hiperlipídica. Após 8 semanas foram avaliados: o ganho de peso, a porcentagem de tecido adiposo, pressão arterial sistólica, frequência cardíaca, perfil lipídico e glicêmico séricos. A partir de cortes histológicos de aortas e corações corados com picrossirius foram feitas análises morfométricas. Em cortes histológicos de aorta foram realizadas a análise fibras elásticas e colágenas usando a coloração de Weigert-Van Gieson. Também foram realizadas a quantificação de fibras colágenas em aortas, usando a coloração de picrossirius. Nos tecidos aórticos e cardíacos foram feitos: 1) Ensaios de atividade enzimática para ECA e MPO. 2) Ensaios de Immunoblotting para a detecção proteíca para ECA e TGF-b. Também foram feitos ensaios de imuno-histoquímica para marcação e localização de ECA e TGF-b no tecido aórtico. / This work evaluated the effect of high-fat diet in mice for the study of cardiovascular inflammation. C57BL / 6 mice at 8 weeks of age were used in the tests were divided in groups control diet and high fat diet. After 8 weeks were evaluated: weight gain, percentage of fat, systolic blood pressure, heart rate, serum lipids and glucose levels. From histological aortas and hearts stained with picrosirius morphometric analyzes. Histological sections of the aorta were performed to analyze elastic and collagen fibers using Weigert-Van Gieson staining. Also the quantification of collagen fibers in aortas using picrosirius staining. In aortic and cardiac tissues were made: 1) Enzymatic activity assays for ACE and MPO. 2) Immunoblotting assays to detect proteinous for ACE and TGF-b. Also were peformed Immunohistochemistry assays for marking and localization of ACE and TGF- b in the aortic tissue.

Intervenções ambientais, como a exposição precoce a estressores ou a dietas ricas em calorias, podem alterar a trajetória da maturação neural e influenciar na susceptibilidade a certas patologias a longo-prazo. Neste contexto, o objetivo do presente estudo foi investigar os efeitos de uma exposição ao isolamento social durante o período pré-pubere associado ou não ao consumo precoce e crônico de uma dieta hiperlipídica (HFD) sobre aspectos cognitivos e emocionais, e possíveis mecanismos neuroquímicos associados a essas alterações, no hipocampo, no córtex pré-frontal e no núcleo accumbens de ratos machos na idade adulta. Os resultados mostraram que os dois fatores, estresse e dieta (separadamente), induziram um comportamento do tipo depressivo nos animais na idade adulta. Além disso, os animais isolados apresentaram um déficit cognitivo associado à memória de curta-duração e de trabalho, enquanto que animais com acesso à HFD demonstraram prejuízo somente na memória de curta-duração. Curiosamente, a interação entre os fatores (estresse e dieta) causou uma reversão dos déficits na memória de curta-duração. Em relação às avaliações do comportamento alimentar hedônico, observamos que o grupo com consumo crônico de HFD apresentou uma menor motivação para obter diferentes tipos de alimentos palatáveis doces. Essa redução motivacional não parece ser associada a uma menor palatabilidade e/ou a uma maior saciedade induzida pela HFD. Em relação aos marcadores de plasticidade analisados no córtex pré-frontal, observamos interações entre os fatores estresse e dieta na atividade da enzima Na+K+-ATPase, nos níveis de BNDF e no imunoconteúdo das proteínas AKT e MAPK/ERK, sendo que os fatores quando aplicados isolados diminuem os níveis dos parâmetros analisados, porém quando associados, os níveis retornam ou aumentam em relação aos valores do grupo controle. O hipocampo foi a estrutura mais afetada pelas intervenções ambientais neste trabalho. Observamos que tanto o estresse, como a dieta hiperlipídica (separadamente) causaram uma redução da plasticidade sináptica hipocampal, por meio de diferentes mecanismos: o acesso crônico à HFD afeta proteínas relacionadas ao funcionamento das sinapses, enquanto o isolamento social parece afetar mais particularmente a via de sinalização do BDNF. Com relação aos achados neuroquímicos no núcleo accumbens, observamos uma redução dos receptores dopaminérgico-1 (D1) e canabinóide-1 (CB1) com o consumo de HFD, enquanto que os animais isolados na pré-puberdade apresentaram uma redução do metabolismo dopaminérgico nesta estrutura. Em suma, esta tese demonstra que tanto o isolamento social e como o consumo contínuo de HFD causam comportamento do tipo depressivo e outras alterações comportamentais, e reduzem marcadores de plasticidade importantes no córtex prefrontal e hipocampo. O acesso à HFD também causa uma menor motivação para o comportamento alimentar hedônico. Assim, tais eventos precoces podem afetar a plasticidade neural levando a importantes alterações comportamentais, e assim predispor a diferentes patologias durante a vida. / Environmental interventions, such as early exposure to stressors or high calorie-diets, can alter the trajectory of neural maturation and influence the susceptibility to some pathologies throughout life. In this context, the aim of the present study was to investigate the effects of exposure to social isolation, during the pre-pubertal period, associated or not with early and chronic consumption of a hyperlipid diet (HFD) on cognitive and emotional aspects, and possible mechanisms associated with these changes, in the hippocampus, the prefrontal cortex and the nucleus accumbens of male rats in adulthood. The results showed that both pre-pubertal social isolation and chronic access to a hyperlipidic diet induced a depressive-like behavior in animals during adulthood. In addition, isolated animals had a cognitive deficit associated with short-term and working memory, whereas animals with access to HFD demonstrated impairment only in short-term memory. Interestingly, the interaction between the factors (stress and diet) caused a reversal in relation to short-term memory, remaining similar to the control group. Regarding the evaluations of the hedonic eating behavior, we observed that HFD group presented a lower motivation to obtain different sweet palatable foods. This impaired motivation does not appear to be associated with less palatability and/or satiety induced by the high-fat diet. Concerning plasticity markers in the prefrontal cortex, we observed interactions between stress and diet on Na+ K+-ATPase activity, BNDF levels and AKT and MAPK/ERK immunocontents. These interactions follow a similar profile: when applied alone, the levels of the analyzed parameters decrease, but when associated, the levels return or increase in relation to the values of the control group. The hippocampus was the structure most affected by the environmental interventions. Both stress and HFD caused a reduction of hippocampal synaptic plasticity through different mechanisms: chronic access to HFD affects proteins related to synaptic function, while social isolation affects the BDNF signaling pathway more significantly. Regarding the neurochemical findings in the nucleus accumbens, we observed a reduction in dopaminergic-1 (D1) and cannabinoid-1 (CB1) receptors with chronic HFD intake, whereas isolated animals had a reduction of dopaminergic metabolism in this same structure. In summary, this thesis shows that both social isolation and chronic consumption of HFD lead to depressive-like behavior and to other behavioral changes; they reduce plasticity markers in prefrontal cortex and hippocampus. HFD access also induced a lower motivation for hedonic feeding. Therefore, these early interventions may affect neural plasticity, leading to important behavioral changes, and thus, predispose to different pathologies later in life.

Introduction: Excessive consumption of high fat, high sugar foods may precipitate cognitive decline. This effect may be more pronounced during cognitive development. The present single-blind randomized controlled trial (RCT) was conducted to examine the effect of a moderate fat, low added sugar (MF/LS) dietary intervention on cognitive function in 8-11 yr old preadolescents with a pre-established high fat, high sugar (HF/HS) dietary pattern. Participants included 17 non-obese (BMI Percentile: 25.4 - 91.3) low to middle income preadolescents randomized to 2 weeks of their usual HF/HS diet (control) or a MF/LS intervention diet. Method: The MF/LS intervention diet was restricted to 25% of calories/day from total fat and <10% of calories from added sugar while the HF/HS control diet was maintained at > 40% of calories/day from total fat and >15.9% of calories from added sugar. All food served was measured to the tenth of a gram. Any uneaten portion of food was weighed to obtain accurate measures of actual intake. NDSR dietary analysis software was used to assess macronutrient, micronutrient and added sugar intakes. Participants were weighed weekly to ensure they remained in energy balance throughout the duration of the study. Pre-post cognitive assessment served as the primary outcome measure. A battery of age appropriate tests from the Penn Computerized Neurocognitive Battery (CNB) as well as the widely used and a previously validated Trail Making task were selected to assess executive function, speed of processing, working memory, attention and spatial ability. Results: Both ANCOVA and a repeated measures approach were used to evaluate the mean difference of post-intervention scores between conditions, controlling for pre-intervention scores and other covariates including age, gender, sleep and mood. For each statistical approach, 10 tests were run, encompassing each of the cognitive assessments given and, for some, their delayed counterpart. Based on the ANCOVA analysis, participants randomized to the MF/LS intervention had a faster median response time (RT) for correct responses on 2 of the 10 tests analyzed, including the initial facial recognition task and its delayed counterpart. Compared to controls, the intervention group displayed 1) a faster total correct RT while controlling for gender (p = 0.02), 2) a faster true negative RT when controlling for gender and age (p = 0.012), and 3) a faster delayed task median total correct RT when controlling for gender and age (p = 0.005). No significant differences between groups were detected for the other assessments. Based on a repeated measures approach, none of the 10 tests analyzed reached statistical significance. Multiple regression analyses revealed a dose response effect on face recognition RT based on % intake of daily calories from total sugar, added sugar, total fat and saturated fat such that a 10% increase in % calories from total sugar, added sugar and saturated fat decreased processing speed for total correct responses on the initial facial recognition task by 0.58 seconds whereas a 10% increase in % total fat decreased processing speed on the same task by 0.44 seconds. The multivariate regression analyses controlled for gender and pretest scores. Conclusions: A 2-week MF/LS dietary intervention may improve delayed face recognition in low to middle income preadolescents with a pre-established HF/HS dietary pattern. Although the intervention appeared to demonstrate a positive effect on 2 measures of cognitive function (initial and delayed facial recognition), after Bonferroni correction, these results only remained significant for the delayed task median total correct RT when controlling for gender and age (p = 0.005). Thus, study results must be interpreted with caution as they may simply be an artifact of chance finding in the ANCOVA statistical analysis. Further investigation of benefits proffered by decreasing % total sugar, % added sugar, % total fat and % saturated fat intake to preadolescent cognition is warranted. Future work should focus on replicating the present study in a larger sample, using hippocampal-dependent specific tasks.

A discussão sobre a efetividade da fortificação dos alimentos com ferro como estratégia para o controle e a redução do risco da anemia vem ganhando novo enfoque, a partir da associação, em estudos epidemiológicos, entre excesso de peso e deficiência de ferro. O conhecimento dos mecanismos de regulação da homeostase de Fe pode contribuir para o entendimento das alterações no status de ferro e sua relação com a adiposidade em indivíduos obesos e com sobrepeso. Neste trabalho, o status de ferro de ratos Wistar, machos e recém-desmamados, alimentados com rações hiperlipídicas foi estudado ao longo de 60 dias. Os animais receberam, ad libitum, rações normo e hiperlipídicas. Um grupo pair-feeding foi usado, que consumiu a mesma quantidade de ferro que o grupo hiperlipídico. Foi observada maior excreção de Iipídeos nas fezes dos animais do grupo HL, em todos os períodos avaliados. Observou-se associação positiva da adiposidade com o conteúdo de Fe no baço, após 15 dias, e com o conteúdo de Fe no fígado após 30 dias, demonstrando que esses tecidos são afetados de maneira diferente pelo consumo da ração hiperlipídica, ao longo do tempo. Após 60 dias, o consumo da ração hiperlipídica resultou em diminuição da sensibilidade à insulina e em aumento da gordura corporal. Nesse período, esses animais apresentaram maior excreção de ferro nas fezes do que os controles. Além disso, houve associação negativa e significativa do ferro sérico com a adiposidade, apesar de não terem sido observadas diferenças na concentração de hemoglobina entre os grupos. Como conclusão, o consumo das rações hiperlipídicas resultou em alterações na digestibilidade do Fe na ração e em redistribuição compartimental do mineral, o que sugere interações entre o ferro e os lipídeos no lúmen intestinal ou, ainda, um processo adaptativo à condição de estresse gerada pelo excesso de lipídeos da dieta. / The discussion on the effectiveness of food fortification with iron as a strategy to control and reduce the risk of anemia is gaining new focus, from the association in epidemiological studies between overweight and iron deficiency. Knowledge on mechanisms of regulation of Fe homeostasis may contribute to the understanding of changes in iron status and its relationship with adiposity in obesity and overweight. In this study, the iron status of weanling male Wistar rats fed with high-fat diets was studied during 60 days. The animals received ad libitum normo-and high-fat diets. A pair-feeding group was used, which consumed the same amount of iron as the HF group. Lipid excretion was higher in feces of the HF group, in ali periods. A positive association between fat and spleen Fe content after 15 days, and the liver Fe content only after 30 days, demonstrate that these tissues are affected differently by the high-fat diet consumption over time. After 60 days, the consumption of high-fat diet resulted in decreased insulin sensitivity and increased fat mass. During this period, these animals had higher iron excretion in feces than controls. In addition, there was a significant negative association between serum iron and adiposity, although no differences were observed in hemoglobin concentration between groups. In conclusion, consumption of high-fat diets resulted in changes in the Fe digestibility and compartmental mineral redistribution, suggesting interactions between iron and lipids in the intestinal lumen, or even an adaptive process to the condition of stress generated by excess of dietary Iipids.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / A menopausa está associada a algumas alterações metabólicas como a obesidade, dislipidemia e inflamação, entre outras anomalias presentes na síndrome metabólica humana. Uma dieta hiperlipídica ou high-fat (HF) associada à menopausa piora tais alterações, aumentando ainda mais o risco de doença cardiovascular. A hipótese de que uma dieta HF agrava as complicações relacionadas à ovariectomia foi testada. Foram avaliadas fêmeas C57BL/6 ovariectomizadas (OVX) ou com operação SHAM e alimentados com ração padrão ou Standard Chow (SC, 10% de gordura) ou uma dieta HF (60% de gordura) por 18 semanas. A eficiência alimentar (EA), massa corporal (MC), distribuição regional das massas de gordura e a morfometria dos adipócitos foram estudados. As análises de sangue (colesterol total, CT, triglicerídeos, TG, citocinas e adipocinas) foram realizadas. Camundongas OVX-HF apresentaram maior EA e maior MC do que os demais grupos (P<0,05). A gordura visceral (ovariana e retroperitoneal) e a gordura subcutânea (gordura inguinal) tiveram o mesmo padrão de distribuição entre os grupos SHAM-SC, SHAM-HF e OVX-SC, mas o grupo OVX-HF apresentou um padrão diferente de acúmulo de gordura - muito maior do que no rupo SHAM-SC. A associação da ovariectomia com a dieta HF aumentou significativamente o diâmetro dos adipócitos dos animais OVX-HF em comparação aos SHAM-HF (P<0,0001) e também agravou a elevação dos níveis de CT, TG e de leptina nas camundongas OVX-HF, em relação aos OVX-SC (P<0,0001). Os níveis de adiponectina foram maiores nas camundongas OVX-SC comparados com as das camundongas SHAM-SC e OVX-HF (P<0,001). A associação da ovariectomia com a dieta HF agravou o aumento dos níveis séricos de leptina em camundongas OVX-HF, em relação aos OVX-SC (P<0,005). TNF-alfa não foi diferente entre os grupos, mas a IL-6 foi significativamente maior nas camundongas OVX-HF comparados a ambos os grupos SHAM-HF e OVX-SC (P<0,0001). Concluindo, a ingestão de uma dieta hiperlipídica por camundongas ovariectomizadas, leva ao aumento do acúmulo e redistribuição inadequada de gordura, à piora dos níveis de citocinas e adipocinas, assim como à desordem metabólica, o que aumenta os fatores de risco para doenças cardiovasculares. / Menopause is associated with some metabolic disorders as dyslipidemia, obesity and inflammation among others abnormalities present in the human metabolic syndrome. High-fat diet (HFD) is associated with menopause enhanced menopause alterations, increasing the risk of cardiovascular disease. The hypothesis that a high-fat (HF) diet aggravates ovariectomy-related complications was tested. SHAM and ovariectomized (OVX) C57BL/6 mice fed standard chow (SC, 10% fat) or a HF diet (60% fat) for 18 weeks were studied. Feed efficiency (FE), body mass (BM), regional fat pad masses distribution and adipocyte morphometry were studied. Blood analyses (total cholesterol, TC, triglycerides, TG, cytokines and adipokines) were performed. OVX-HF mice had greater FE and BM than all other groups (P<0.05). Visceral fat (ovarian and retroperitoneal fat pads) and the subcutaneous fat (inguinal fat pad) varied with a parallel pattern of fat accumulation in SHAM-SC, SHAM-HF and OVX-SC, but OVX-HF had different pattern of fat accumulation much greater than in SHAM-SC. The association of ovariectomy with HF diet increased significantly the adipocyte diameter in OVX-HF in comparison with SHAM-HF mice (P<0.0001) and also aggravated the increment of TC, TG and leptin levels in OVX-HF mice in comparison to OVX-SC mice (P<0.0001). Adiponectin levels were higher in OVX-SC mice compared to both SHAM-SC and OVX-HF mice (P<0.001). The association of ovariectomy with HF diet aggravated the increase of serum leptin levels in OVX-HF mice in relation to OVX-SC mice (P<0.005). TNF-alpha was not different among the groups, but IL-6 was markedly higher in OVX-HF mice than in both SHAM-HF and OVX-SC mice (P<0.0001). In conclusion, high-fat diet intake worsens, in ovariectomized mice, the fat accumulation and redistribution as well as the cytokines and adipokines levels, and metabolic disorder, which increases risk factors for cardiovascular diseases.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / No presente estudo, foram investigados o mecanismo central e a termogênese pelo tecido adiposo marrom (BAT) envolvidos com a perda de massa corporal (MC) observada com a administração de liraglutida (análoga do hormônio GLP1). Camundongos machos C57BL/6, foram alimentados com dieta padrão e tratados com veículo (SC) ou com liraglutida (SC/Lir) ou com dieta hiperlipídica e tratados com veículo (HF) ou com liraglutida (HF/Lir) Nossos resultados demostram que a administração de liraglutida aumentou o neuropeptídeo anorexigênico pro-opiomelanocortina no hipotálamo e diminuiu a expressão do mRNA da proteína supressora da sinalização de citocinas-3. A administração de liraglutida melhorou os níveis plasmáticos de adiponectina e diminuiu tanto a intolerância à glicose, como a resistência à insulina. Além do mais, tanto o grupo SC como o grupo HF, consumiram a mesma quantidade de comida, já o grupo SC/Lir comeu 17,5 menos comida comparado com o grupo SC e, da mesma forma, o grupo HF/lir diminuiu o consumo alimentar em 22,5% comparado com o grupo HF. A massa corporal final foi 8,5% menor no grupo SC/Lir comparado com o grupo SC e 16% menor no grupo HF comparado com o grupo HF/Lir. Além do mais, a administração de liraglutida aumentou o consumo de oxigênio e a produção de dióxido de carbono, e diminuiu o quociente respiratório. A liraglutida aumentou ainda os níveis do receptor beta 3 adrenérgico, da proteína desacopladora mitocondrial-1, do TC10 e do transportador de glicose estimulado pela insulina (GLUT)-4 no BAT. Em conclusão, a administração de liraglutida em camundongos obesos induzidos por dieta ativou a via anorexigênica, diminuindo o consumo alimentar, atuando sinergicamente com o aumento do gasto energético.