Impacto da ingestão de dieta hipercalórica sobre respostas comportamentais, endócrinas e cardíacas ao estresse
Arquivos
Data
2015-06-30
Autores
Ortolani, Daniela 
Orientadores
Spadari, Regina Celia
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
No Capítulo I desta tese, avaliamos parâmetros comportamentais, endócrinos e metabólicos de ratos submetidos ao estresse crônico brando e imprevisível (ECBI), com acesso à ração comercial ou ração comercial e dieta hipercalórica (comfort food). O estresse não alterou a preferência por comfort food mas diminuiu a ingestão de ambas as dietas. No teste do labirinto em cruz elevado (LCE), os ratos submetidos ao ECBI diminuíram a porcentagem de tempo e de entradas nos braços abertos, com efeitos opostos nos braços fechados quando comparados com os ratos controles, ambas condições mais pronunciadas em ratos com acesso à comfort food. No teste do campo aberto, o ECBI diminuiu o tempo no centro, independente da dieta; nem o estresse ou a dieta afetaram o número de cruzamentos, levantamentos ou episódios de auto-limpezas. O aumento da corticosterona sérica induzido pelo estresse foi atenuado em ratos alimentados com comfort food. A concentração sérica de triacilglicerol não foi afetada pelo estresse ou dieta, no entanto o acesso à comfort food aumentou as concentrações séricas de colesterol total e glicose. Conclui-se que o ECBI tem um efeito anorexigênico e que o estresse crônico e a ingestão de comfort food induziram um perfil ansiogênico apesar da comfort food ter atenuado a resposta endócrina de estresse. Os presentes dados indicam que a combinação do estresse e o acesso à comfort food, ambos aspectos comuns da vida moderna, podem constituir uma ligação entre o estresse, comportamento alimentar e ansiedade. No capítulo II, avaliamos um modelo comportamental bioinformatizado (Home-cage Monitoring system, HCM) em camundongos C57BL/6J tratados cronicamente com corticosterona na água de beber. O tratamento com corticosterona aumentou a ingestão alimentar e líquida, diminuiu a atividade locomotora, aumentou a adiposidade, aumentou as concentrações plasmáticas de corticosterona, leptina, insulina e triacilglicerol, diminuiu a de grelina e não alterou a glicemia. Com relação a expressão de RNAm dos peptídeos hipotalâmicos, a corticosterona aumentou o peptídeo relacionado com a proteína Agouti (AgRP) e diminuiu o neuropeptídeo Y (NPY). Os outros neupeptídeos, hormônio liberador de corticotrofina (CRH), proopimelanocortina (POMC) e vasopresina (AVP) não foram alterados. A corticosterona produziu alterações substanciais nos padrões circadianos do comportamento. Nos comportamentos avaliados no HCM system, houve diminuição na probabilidade do estado ativo na fase escura e aumento no início da fase clara resultante da redução da duração do estado ativo na fase escura e aumento da taxa do estado ativo no início da fase clara. Essa redução da probabilidade do estado ativo durante a fase escura foi devido a diminuição da locomoção nesta fase. O aumento da probabilidade do estado ativo no início da fase clara foi devido ao aumento da duração e tamanho dos surtos de ingestão alimentar e líquida durante esta fase. A corticosterona diminuiu o tempo de exploração do novo objeto na caixa-moradia após 30 min de exposição. Os resultados mostraram diversas consequências comportamentais, endócrinas e metabólicas da exposição a elevadas concentrações de corticosterona avaliadas no HCM system. Além disso, revelou meios intrigantes e altamente específicos de como o tratamento com corticosterona altera os padrões comportamentais e sua regulação circadiana. No Capítulo III, investigamos a expressão gênica e protéica dos adrenoceptores beta (beta-ARs) em ventrículos esquerdos de ratos submetidos ao ECBI com acesso à dieta hiperlipídica. O ECBI e o acesso à comfort food não alteraram a expressão gênica dos beta1-AR, mas a expressão protéica apresentou-se diminuída nos ratos submetidos ao ECBI. Com relação à população dos beta2ARs, nem o estresse e a dieta alteraram a expressão gênica e protéica. Acreditamos que essa alteração na razão beta1/2-ARs seja resultado de mecanismo adaptativo do tecido cardíaco frente à situações de estresse, e que a ingestão de dieta hiperlídica apesar de reduzir as concentrações séricas de corticosterona induzida pelo estresse, não foi eficiente para alterar a expressão dos beta-ARs. No entanto, as consequências destas alterações sobre a função cardíaca devem ser investigadas.
In Chapter I of this thesis, we evaluated behavioral, endocrine and metabolic parameters of rats submitted to chronic unpredictable and mild stress (CUMS), with access to commercial food or commercial food and hyperlipidic diet (comfort food). Stress did not change the preference for comfort food but decreased the food intake of both diets. In the elevated plus maze test (EPM), rats submitted to CUMS decreased the percentage of time and entries into the open arms, with opposite effects in the closed arms when compared with the control rats, both conditions were more pronounced in rats with access to comfort food. In the open field test, the CUMS decreased the time in the center, regardless of the diet; either stress or diet affected the number of crossings, rearings or episodes of grooming. The increase in serum corticosterone induced stress was attenuated in mice fed food comfort. The serum triglyceride was not affected by stress or diet, however access to comfort food increased serum concentration of total cholesterol and glucose. It concludes that the CUMS has a anorexigenic effect and that chronic stress and food intake of comfort food induced an anxiogenic profile despite the comfort food have atenuated the endocrine response to stress. The present data indicate that the combination of stress and access to comfort food, both common aspects of modern life, may be a link between stress, eating behavior and anxiety. In Chapter II, we evaluated a behavioral bioinformatic approach (Homecage Monitoring System, HCM) in C57BL/6J mice chronically treated with corticosterone in their drinking water. Treatment with corticosterone increased food and liquid intake, decreased locomotor activity, increased adiposity, increased plasmatic concentrations of corticosterone, leptin, insulin and triacylglicerol, decreased ghrelin and did not alter blood glucose. With respect mRNA expression of hypothalamic peptides, corticosterone increased the Agouti related protein (AgRP) and decreased the neuropeptide Y (NPY). The other neupeptídeos, corticotrophin release hormone (CRH), proopiomelanocortin (POMC) and vasopressin (AVP) have not changed. The corticosterone treatment produced substantial changes in circadian behavior patterns. Behaviors evaluated in HCM system, there was a decrease in the probability of active state in the dark phase and increase in the beginning of the light phase resulting in the reduction of duration of the active state. This probability reduction in the active state during the dark phase was due to decreased of locomotion in this phase. The increase of probability in the active state at the beginning of the light phase was due to increase of duration and size of food and liquid intake during this phase. The corticosterone decreased the time of exploration of the new object in the home cage after 30 min of exposure. The results showed several behavioral, endocrine and metabolic consequences of exposure to elevated corticosterone concentrations evaluated in HCM system. Moreover, it reveled intriguing and highly specific how the corticosterone treatment alters the circadian behavioral patterns and their regulation. In Chapter III, we investigated the gene and protein expression of betaadrenoceptor (βARs) in left ventrycles of rats submitted to CUMS with access to hyperlipidic diet. The CUMS and the access to comfort food did not alter the gene expression of β1AR, but the protein expression decreased in rats submitted to CUMS. Regarding the population of β2ARs, neither stress or diet altered the gene and protein expression. We believe that the change in the ratio of β1 and β2ARs is the result of adaptive mechanism of cardiac tissue due stressful situations, and that hyperlipidic diet intake while to reduce the serum corticosterone induced by stress, it was not efficient to change the expression of βARs. However, the consequences of these changes on the cardiac function should be investigated.
In Chapter I of this thesis, we evaluated behavioral, endocrine and metabolic parameters of rats submitted to chronic unpredictable and mild stress (CUMS), with access to commercial food or commercial food and hyperlipidic diet (comfort food). Stress did not change the preference for comfort food but decreased the food intake of both diets. In the elevated plus maze test (EPM), rats submitted to CUMS decreased the percentage of time and entries into the open arms, with opposite effects in the closed arms when compared with the control rats, both conditions were more pronounced in rats with access to comfort food. In the open field test, the CUMS decreased the time in the center, regardless of the diet; either stress or diet affected the number of crossings, rearings or episodes of grooming. The increase in serum corticosterone induced stress was attenuated in mice fed food comfort. The serum triglyceride was not affected by stress or diet, however access to comfort food increased serum concentration of total cholesterol and glucose. It concludes that the CUMS has a anorexigenic effect and that chronic stress and food intake of comfort food induced an anxiogenic profile despite the comfort food have atenuated the endocrine response to stress. The present data indicate that the combination of stress and access to comfort food, both common aspects of modern life, may be a link between stress, eating behavior and anxiety. In Chapter II, we evaluated a behavioral bioinformatic approach (Homecage Monitoring System, HCM) in C57BL/6J mice chronically treated with corticosterone in their drinking water. Treatment with corticosterone increased food and liquid intake, decreased locomotor activity, increased adiposity, increased plasmatic concentrations of corticosterone, leptin, insulin and triacylglicerol, decreased ghrelin and did not alter blood glucose. With respect mRNA expression of hypothalamic peptides, corticosterone increased the Agouti related protein (AgRP) and decreased the neuropeptide Y (NPY). The other neupeptídeos, corticotrophin release hormone (CRH), proopiomelanocortin (POMC) and vasopressin (AVP) have not changed. The corticosterone treatment produced substantial changes in circadian behavior patterns. Behaviors evaluated in HCM system, there was a decrease in the probability of active state in the dark phase and increase in the beginning of the light phase resulting in the reduction of duration of the active state. This probability reduction in the active state during the dark phase was due to decreased of locomotion in this phase. The increase of probability in the active state at the beginning of the light phase was due to increase of duration and size of food and liquid intake during this phase. The corticosterone decreased the time of exploration of the new object in the home cage after 30 min of exposure. The results showed several behavioral, endocrine and metabolic consequences of exposure to elevated corticosterone concentrations evaluated in HCM system. Moreover, it reveled intriguing and highly specific how the corticosterone treatment alters the circadian behavioral patterns and their regulation. In Chapter III, we investigated the gene and protein expression of betaadrenoceptor (βARs) in left ventrycles of rats submitted to CUMS with access to hyperlipidic diet. The CUMS and the access to comfort food did not alter the gene expression of β1AR, but the protein expression decreased in rats submitted to CUMS. Regarding the population of β2ARs, neither stress or diet altered the gene and protein expression. We believe that the change in the ratio of β1 and β2ARs is the result of adaptive mechanism of cardiac tissue due stressful situations, and that hyperlipidic diet intake while to reduce the serum corticosterone induced by stress, it was not efficient to change the expression of βARs. However, the consequences of these changes on the cardiac function should be investigated.
Descrição
Citação
ORTOLANI, Daniela. Impacto da ingestão de dieta hipercalórica sobre respostas comportamentais, endócrinas e cardíacas de estresse. 2015. 134 f. Tese (Doutorado em Farmacologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.