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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

Proliferação e diferenciação in vitro de células mononucleares medulares após estímulo com fatores de crescimento em ratos Wistar submetidos à dieta hiperlipídica / Proliferation and differentiation of bone marrow mononuclear cells in vitro after stimulation with growth factors in Wistar rats subjected to high fat diet

Carmo, Luciana Simão do 16 March 2012 (has links)
O aumento da adiposidade corpórea pode gerar diversos mediadores inflamatórios com capacidade de influenciar a proliferação e a diferenciação hematopoética e, consequentemente, a complexa regulação da hematopoese. Por isso, propusemo-nos, neste trabalho, avaliar a influência do aumento da adiposidade corpórea sobre a proliferação e a diferenciação de células hematopoéticas, bem como sua capacidade em sintetizar citocinas. Ratos Wistar, machos foram alimentados com uma dieta rica em lipídios durante 14 semanas. Após esse período foram avaliados hemograma, mielograma, perfil lipídico, concentrações séricas de leptina, insulina e adiponectina. Citômetria de fluxo foi utilizada para avaliação da porcentagem de células CD34+/CD133+, bem como o ciclo celular de células medulares. Células medulares foram utilizadas para avaliar a atividade proliferativa in vitro e a capacidade de diferenciação, in vitro, na presença de IL-3, EPO, GM-CSF e G-CSF. Animais, alimentados com dieta hiperlipídica, apresentaram maiores concentrações de leptina circulante, com aumento de gordura corporal, aumento da concetração de proteína C reativa, colesterol total, LDL, VLDL e triacilglicerol. O hemograma apresentou neutrofilia absoluta e a medula óssea apresentou-se hipercelular com aumento do número de granulócitos maduros e da população celular CD133-/CD34+. Os resultados dos testes in vitro demonstraram aumento da capacidade de síntese de IL-3 e aumento de G-CSF, com aumento do potencial proliferativo, também evidenciado pelo maior número de células medulares na fase S/G2/M, bem como o aumento da diferenciação granulocítica. Esses resultados sugerem que a leucocitose e neutrofilia observadas em situações de aumento da adiposidade corpórea são decorrentes de uma complexa modulação do sistema hematopoético. / The body fat increase can generate various inflammatory mediators, that are capable to influence the proliferation and differentiation of hematopoietic cells and consequently modulate the complex regulation of the hematopoiesis. In this study we have proposed to evaluate the effect of increase body fat on the proliferation and differentiation of hematopoietic cells, as well as its ability to synthesize cytokines. Male Wistar rats were subjected to a high fat diet during a period of 14 weeks. After that period were evaluated hemogram, mielogram, lipid profile and the serum concentrations of leptin, insulin and adiponectin. Flow cytometry was used to evaluate the percentage of CD34+/CD133+, as well as the cell cycle of bone marrow cells. Bone marrow cells were used to perform the proliferation and differentiation capacity in vitro in the presence of IL-3, EPO, GM-CSF and G-CSF. Animals fed high-fat diet had higher concentrations of circulating leptin with increase body fat, and increase of C-reactive protein, total cholesterol, LDL, VLDL and triacylglycerol concentrations. The hemogram showed absolute neutrophilia and a hypercellular bone marrow with increase of granulocytic mature population and CD133-/CD34+ cells. The results in vitro, showed an increase of IL-3 and G-CSF production, and higher proliferative potential with an increase in S/G2/M bone marrow cell cycle phases, as well as an increase of the granulocytic differentiation. The results suggest that leukocytosis and neutrophilia observed in this model of body fat increase are in fact a result of a complex modulation of the hematopoietic system.
12

Influência do tempo de exposição à obesidade sobre a expressão gênica e protéica do sistema regulador do trânsito de cálcio miocárdico

Leopoldo, Ana Paula Lima [UNESP] 18 February 2010 (has links) (PDF)
Made available in DSpace on 2014-06-11T19:31:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-18Bitstream added on 2014-06-13T19:40:53Z : No. of bitstreams: 1 leopoldo_apl_dr_botfm.pdf: 2253115 bytes, checksum: 28ca3088b9d995d2eab4a88eb473ac7d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Atualmente mais de um bilhão de pessoas apresentam sobrepeso, sendo que, mais de 30% desta população é obesa. Diversas alterações estruturais e funcionais do coração em humanos tem sido frequentemente associadas com a obesidade. Modelos experimentais, por dieta hiperlipídica, têm sido utilizados para estudar a relação obesidade e coração. O trânsito de cálcio miocárdico tem sido extensivamente estudado em diversos modelos experimentais e frequentemente relacionado com disfunção cardíaca. Entretanto, a literatura mostra escassez de estudos que avaliaram a relação entre o tempo de exposição à obesidade por dieta hiperlipídica, o RNAm e as proteínas envolvidas na homeostase de Ca+2 miocárdico. Além disso, pesquisas relatam a influência dos hormônios tireoidianos nestas proteínas, podendo acarretar alterações na contração e relaxamento cardíaco.O objetivo principal desse estudo foi testar a hipótese que o aumento no tempo de exposição à obesidade acarreta diminuição na expressão e/ou fosforilação das proteínas e dos respectivos níveis de RNAm relacionados com o trânsito de Ca+2 miocárdico. Este estudo teve como objetivo secundário constatar se a diminuição na expressão gênica foi acompanhada de redução dos níveis hormonais tireoidianos. Os períodos de dieta hiperlipídica, utilizados nesse estudo, foram eficientes em promover obesidade, desde que o índice de adiposidade utilizado para caracterizar os animais como obesos foi 79,5%, 82% e 69,5% maior do que os respectivos controles, após 15, 30 e 45 semanas. O tempo de exposição à dieta hiperlipídica não promoveu alterações na gordura corporal total entre os grupos obesos; este resultado indica que, neste trabalho, não houve aumento na intensidade da obesidade ao longo do tempo. Neste estudo foram visualizadas algumas comorbidades frequentemente associadas com a obesidade... / Currently, greater than one billion people are overweight and 30% of the population is obese. Several structural and functional changes of the heart have often been associated with human obesity. Experimental models for high-fat diets have been used to study the relationship between obesity and the heart. Myocardial calcium (Ca2+) handling has been extensively studied in several experimental models and has often been shown to be related to cardiac dysfunction. However, few studies have evaluated the relationship between the duration of exposure to obesity and a high-fat diet, and mRNA and proteins involved in homeostasis of myocardial Ca2+. Some studies have reported the influence of thyroid hormones on these proteins, which may cause changes in cardiac contraction and relaxation. The main objective of the current study was to test the hypothesis that the increased duration of exposure to obesity leads to a reduction in the expression and/or phosphorylation of proteins and mRNA levels related to myocardial Ca2+ handling. This study had, as additional objective, to verify if the decrease in mRNA expression was accompanied by a reduction in thyroid hormone levels. The periods of exposure to a high-fat diet used in this study were effective in promoting obesity since the adiposity index used to characterize animals as obese was 79.5%, 82%, and 69.5% higher than controls after 15, 30, and 45 weeks, respectively. The duration of exposure to a high-fat diet did not change the total body fat between the obese groups. This result indicates that there was not an increase in the intensity of obesity over time. In this study, some co-morbidities often associated with experimental obesity existed, such as glucose intolerance, insulin resistance, hyperinsulinemia, hyperleptinemia, and dyslipidemia; however, the co-morbidities were not associated with changes in systolic blood pressure ...(Complete abstract click electronic access below)
13

Examining the Effects of a High Fat Diet on the Development of Metabolic Syndrome and Gut Leakiness in Male Sprague-Dawley Rats

January 2019 (has links)
abstract: The prevalence of obesity and obesity-related disorders have increased world-wide. In the last decade, the intestinal microbiome has become a major indicator of metabolic and gastrointestinal health. Previous research has shown that high-fat diet (HFD) consumption can alter the microbial composition of the gut by increasing the abundance of gram-positive bacteria associated with the onset of obesity and type 2 diabetes. Although, the most common form of obesity and metabolic syndrome intervention is exercise and diet, these recommendations may not improve severe cases of obesity. Thus, an important relevance of my project was to investigate whether the intake of an organometallic complex (OMC) would prevent the onset of metabolic and gastrointestinal complications associated with high-fat diet intake. I hypothesized that the consumption of a HFD for 6 weeks would promote the development of metabolic and gastrointestinal disease risk factors. Next, it was hypothesized that OMC treatment would decrease metabolic risk factors by improving insulin sensitivity and decreasing weight gain. Finally, I hypothesized that HFD-intake would increase the abundance of gram-positive bacteria associated with gastrointestinal disease. My preliminary data investigated the effects of a 6-week HFD on the development of hepatic steatosis, intestinal permeability and inflammation in male Sprague Dawley rats. I found that a 6-week HFD increases hepatic triglyceride concentrations, plasma endotoxins and promotes the production of pro-inflammatory cytokines in the cecum wall. I then investigated whether OMC treatment could prevent metabolic risk factors in male Sprague-Dawley rats fed a HFD for 10 weeks and found that OMC can mitigate risk factors such hyperglycemia, liver disease, impaired endothelial function, and inflammation. Lastly, I investigated the effects of a 10-week HFD on the gastrointestinal system and found an increase in liver triglycerides and free glycerol and alterations of the distal gut microbiome. My results support the hypothesis that a HFD can promote metabolic risk factors, alter the gut microbiome and increase systemic inflammation and that OMC treatment may help mitigate some of these effects. Together, these studies are among the first to demonstrate the effects of a soil-derived compound on metabolic complications. Additionally, these conclusions also provide an essential basis for future gastrointestinal and microbiome studies of OMC treatment. / Dissertation/Thesis / Doctoral Dissertation Biology 2019
14

Binge-eating behavior in mice: influences of restriction and palatability in a limited access model

Davis, Kristina W. 15 May 2009 (has links)
Animal models of bingeing have typically used stress to induce bingeing. A recent model, limited-access to high-fat diet (HFD), has shown that caloric restriction and stress were not required to induce bingeing in rats. This study replicated this model in mice, explored the fat content within the model, and investigated locomotor activation associated with binge-eating. Adult mice were maintained on a restricted feeding (RF) schedule of 2 h/d of access to chow or ad lib access to chow, and then provided limited access to 45% HFD or 84% HFD for 30 min 3 d/ week for 6 total snack sessions. Circadian activity was monitored for RF animals offered 84% HFD, and after 6 snack sessions were complete, allowed continuous access to the 45% HFD or the 84% HFD for two weeks to explore rebound feeding. Bingeing, defined by increasing intakes across days, was reported for mice offered 45% HFD regardless of deprivation state (RF or ad lib), while mice offered 84% HFD only exhibited bingeing when they were restricted. Comparison of male and female mice maintained RF, offered 45% HFD snack, showed that females had higher intake (kcals/g-bw) while ad lib fed mice exhibited no sex differences. Circadian recordings for female RF mice offered 84% HFD showed shifts in activity from the first hour of dark cycle to the hour preceding the snack and supported that offering the HFD produced alterations in food-associated arousal. During rebound, female RF mice given 84% HFD showed the highest intakes in week 1, and then exhibited a marked decline in week 2. The week 1 intake for RF animals were to regain lost body weight and that homeostatic-like intake in week 2 allowed normal body weight maintenance. Results of this investigation support human data that females are more susceptible to binge-type eating disorder, shows that limited access to palatable foods for females under caloric restriction induces changes in circadian activity, and reveals that using mice in this model requires more investigation to optimize binge-behavior. Diet comparisons also suggest that homeostatic and reward mechanisms may have an additive effect on bingeing.
15

Regulation of hepatic inflammatory response and lipid metabolism in metabolic disease

Wu, Nan 10 1900 (has links)
Hyperhomocysteinemia, an elevation of blood homocysteine levels, is a metabolic disorder associated with dysfunction of multiple organs. Previous studies have shown that hyperhomocysteinemia is related to fatty liver. However, the underlying mechanism remains speculative. The objective of the present study is to investigate the regulatory mechanism of hepatic inflammatory response and cholesterol metabolism during metabolic disorders. In the present study, hyperhomocysteinemia was induced in Sprague-Dawley rats by feeding a high-methionine diet. The mRNA and protein expression of cyclooxygenase-2 (COX-2), a pro-inflammatory factor, were significantly elevated in the liver of hyperhomocysteinemic rats. An activation of NF-B and a stimulation of oxidative stress were observed in the same liver tissue in which COX-2 was induced. Inhibition of NF-B or oxidative stress effectively abolished hepatic COX-2 expression, inhibited the formation of inflammatory foci, and improved liver function. Activity of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis, was markedly elevated in the liver of hyperhomocysteinemic rats, which may contribute to the hepatic lipid accumulation induced by hyperhomocysteinemia. Administration of Berberine (5mg/ kg body weight/ day for 5 days) inhibited HMG-CoA reductase activity via upregulating AMP-activated protein kinase (AMPK)-mediated phosphorylation of HMG-CoA reductase. Berberine treatment reduced hepatic cholesterol content and ameliorated liver function. In addition, the regulatory mechanism of HMG-CoA reductase activation was investigated in C57BL/6 mice fed a high-fat diet. There was a significant increase in hepatic HMG-CoA reductase mRNA and protein expression as well as enzyme activity. The DNA binding activity of sterol regulatory element binding protein (SREBP)-2 (a transcription factor of HMG-CoA reductase) and Sp1 (a transcription factor of SREBP-2) were both increased in the liver of mice fed a high-fat diet. The in vitro study in palmitic acid-treated HepG2 cells further confirmed that inhibition of Sp1 by siRNA transfection abolished palmitic acid-induced SREBP-2 and HMG-CoA reductase mRNA expression. In conclusion, the present study have demonstrated that (1) Hepatic COX-2 expression is induced via oxidative stress mediated NF-B activation during hyperhomocysteinemia; (2) Dietary berberine reduces cholesterol biosynthesis by elevating AMPK-mediated HMG-CoA reductase phosphorylation; (3) HMG-CoA reductase is upregulated by Sp1-mediated SREBP-2 activation in the liver during high-fat diet feeding.
16

Does moderate intensity exercise in the postprandial period attenuate the inflammatory response to a high-fat meal?

Teeman, Colby S. January 1900 (has links)
Master of Science / Department of Human Nutrition / Sara K. Rosenkranz / Background: High-fat meals (HFM) have been shown to increase postprandial lipemia (PPL) and inflammation. Acute exercise both pre and post-meal has been shown to attenuate PPL and inflammation. However, studies examining the interaction of HFMs and exercise on PPL and inflammation have used meal and exercise conditions more extreme than typical for average adults. The purpose of this study was to determine if moderate intensity exercise following a "true-to-life" HFM would attenuate PPL and inflammation. Methods: Participants were thirty-nine young adults (18-40 years) with no known metabolic disease. Inclusion criteria consisted of participants meeting physical activity guidelines of ≥ 150 min/week of moderate-to-vigorous physical activity or ≥ 75 min/week of vigorous activity, or < 30 min of planned physical activity per week. Participants were block randomized to EX or CON groups. Participants consumed a HFM of 10 kcal/kgbw. The EX group walked at 60% VO[subscript 2peak] to expend ≈ 5 kcal/kgbw beginning one-hour following the HFM. The CON group remained sedentary during the postprandial period. Blood samples were collected at baseline and 2, and 4hrs postprandially. Results: At baseline, there were no differences between EX and CON groups for any metabolic or inflammatory markers (p>0.05). Postprandial TRG increased ≈ 100% (p<0.001) in both groups, with no differences between groups. HDL concentrations decreased across time in both groups (p<0.001) with no differences between groups (p=0.338). HDL was higher in the EX group at 2hrs (p=0.047), but not 4hrs (p=0.135). IL-6 and TNF-α concentrations did not change over time with no differences between groups (p>0.05). The EX group increased sVCAM-1 from baseline to 4hr (p=0.003), while the CON group did not. Change in TRG was associated with change IL-6, IL-8, IL-10 and TNF-α from baseline to 2hrs when controlling for VO[subscript 2peak] and body fat%. No other associations were seen between change scores for TRG and inflammatory markers. Conclusions: Despite significant increases in PPL following a HFM, moderate intensity exercise in the postprandial period did not mitigate the PPL nor the inflammatory response to the HFM. These results indicate PPL and inflammation following a HFM are not directly related in a young, healthy population with low metabolic risk.
17

Influência do tempo de exposição à obesidade sobre a expressão gênica e protéica do sistema regulador do trânsito de cálcio miocárdico /

Leopoldo, Ana Paula Lima. January 2010 (has links)
Resumo: Atualmente mais de um bilhão de pessoas apresentam sobrepeso, sendo que, mais de 30% desta população é obesa. Diversas alterações estruturais e funcionais do coração em humanos tem sido frequentemente associadas com a obesidade. Modelos experimentais, por dieta hiperlipídica, têm sido utilizados para estudar a relação obesidade e coração. O trânsito de cálcio miocárdico tem sido extensivamente estudado em diversos modelos experimentais e frequentemente relacionado com disfunção cardíaca. Entretanto, a literatura mostra escassez de estudos que avaliaram a relação entre o tempo de exposição à obesidade por dieta hiperlipídica, o RNAm e as proteínas envolvidas na homeostase de Ca+2 miocárdico. Além disso, pesquisas relatam a influência dos hormônios tireoidianos nestas proteínas, podendo acarretar alterações na contração e relaxamento cardíaco.O objetivo principal desse estudo foi testar a hipótese que o aumento no tempo de exposição à obesidade acarreta diminuição na expressão e/ou fosforilação das proteínas e dos respectivos níveis de RNAm relacionados com o trânsito de Ca+2 miocárdico. Este estudo teve como objetivo secundário constatar se a diminuição na expressão gênica foi acompanhada de redução dos níveis hormonais tireoidianos. Os períodos de dieta hiperlipídica, utilizados nesse estudo, foram eficientes em promover obesidade, desde que o índice de adiposidade utilizado para caracterizar os animais como obesos foi 79,5%, 82% e 69,5% maior do que os respectivos controles, após 15, 30 e 45 semanas. O tempo de exposição à dieta hiperlipídica não promoveu alterações na gordura corporal total entre os grupos obesos; este resultado indica que, neste trabalho, não houve aumento na intensidade da obesidade ao longo do tempo. Neste estudo foram visualizadas algumas comorbidades frequentemente associadas com a obesidade ...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Currently, greater than one billion people are overweight and 30% of the population is obese. Several structural and functional changes of the heart have often been associated with human obesity. Experimental models for high-fat diets have been used to study the relationship between obesity and the heart. Myocardial calcium (Ca2+) handling has been extensively studied in several experimental models and has often been shown to be related to cardiac dysfunction. However, few studies have evaluated the relationship between the duration of exposure to obesity and a high-fat diet, and mRNA and proteins involved in homeostasis of myocardial Ca2+. Some studies have reported the influence of thyroid hormones on these proteins, which may cause changes in cardiac contraction and relaxation. The main objective of the current study was to test the hypothesis that the increased duration of exposure to obesity leads to a reduction in the expression and/or phosphorylation of proteins and mRNA levels related to myocardial Ca2+ handling. This study had, as additional objective, to verify if the decrease in mRNA expression was accompanied by a reduction in thyroid hormone levels. The periods of exposure to a high-fat diet used in this study were effective in promoting obesity since the adiposity index used to characterize animals as obese was 79.5%, 82%, and 69.5% higher than controls after 15, 30, and 45 weeks, respectively. The duration of exposure to a high-fat diet did not change the total body fat between the obese groups. This result indicates that there was not an increase in the intensity of obesity over time. In this study, some co-morbidities often associated with experimental obesity existed, such as glucose intolerance, insulin resistance, hyperinsulinemia, hyperleptinemia, and dyslipidemia; however, the co-morbidities were not associated with changes in systolic blood pressure ...(Complete abstract click electronic access below) / Orientador: Antonio Carlos Cicogna / Coorientador: Patrícia Chakur Brum / Banca: Alessandra Medeiros / Banca: Carlos Eduardo Negrão / Banca: Célia Regina Nogueira / Banca: Maeli Dal Pai Silva / Doutor
18

Proliferação e diferenciação in vitro de células mononucleares medulares após estímulo com fatores de crescimento em ratos Wistar submetidos à dieta hiperlipídica / Proliferation and differentiation of bone marrow mononuclear cells in vitro after stimulation with growth factors in Wistar rats subjected to high fat diet

Luciana Simão do Carmo 16 March 2012 (has links)
O aumento da adiposidade corpórea pode gerar diversos mediadores inflamatórios com capacidade de influenciar a proliferação e a diferenciação hematopoética e, consequentemente, a complexa regulação da hematopoese. Por isso, propusemo-nos, neste trabalho, avaliar a influência do aumento da adiposidade corpórea sobre a proliferação e a diferenciação de células hematopoéticas, bem como sua capacidade em sintetizar citocinas. Ratos Wistar, machos foram alimentados com uma dieta rica em lipídios durante 14 semanas. Após esse período foram avaliados hemograma, mielograma, perfil lipídico, concentrações séricas de leptina, insulina e adiponectina. Citômetria de fluxo foi utilizada para avaliação da porcentagem de células CD34+/CD133+, bem como o ciclo celular de células medulares. Células medulares foram utilizadas para avaliar a atividade proliferativa in vitro e a capacidade de diferenciação, in vitro, na presença de IL-3, EPO, GM-CSF e G-CSF. Animais, alimentados com dieta hiperlipídica, apresentaram maiores concentrações de leptina circulante, com aumento de gordura corporal, aumento da concetração de proteína C reativa, colesterol total, LDL, VLDL e triacilglicerol. O hemograma apresentou neutrofilia absoluta e a medula óssea apresentou-se hipercelular com aumento do número de granulócitos maduros e da população celular CD133-/CD34+. Os resultados dos testes in vitro demonstraram aumento da capacidade de síntese de IL-3 e aumento de G-CSF, com aumento do potencial proliferativo, também evidenciado pelo maior número de células medulares na fase S/G2/M, bem como o aumento da diferenciação granulocítica. Esses resultados sugerem que a leucocitose e neutrofilia observadas em situações de aumento da adiposidade corpórea são decorrentes de uma complexa modulação do sistema hematopoético. / The body fat increase can generate various inflammatory mediators, that are capable to influence the proliferation and differentiation of hematopoietic cells and consequently modulate the complex regulation of the hematopoiesis. In this study we have proposed to evaluate the effect of increase body fat on the proliferation and differentiation of hematopoietic cells, as well as its ability to synthesize cytokines. Male Wistar rats were subjected to a high fat diet during a period of 14 weeks. After that period were evaluated hemogram, mielogram, lipid profile and the serum concentrations of leptin, insulin and adiponectin. Flow cytometry was used to evaluate the percentage of CD34+/CD133+, as well as the cell cycle of bone marrow cells. Bone marrow cells were used to perform the proliferation and differentiation capacity in vitro in the presence of IL-3, EPO, GM-CSF and G-CSF. Animals fed high-fat diet had higher concentrations of circulating leptin with increase body fat, and increase of C-reactive protein, total cholesterol, LDL, VLDL and triacylglycerol concentrations. The hemogram showed absolute neutrophilia and a hypercellular bone marrow with increase of granulocytic mature population and CD133-/CD34+ cells. The results in vitro, showed an increase of IL-3 and G-CSF production, and higher proliferative potential with an increase in S/G2/M bone marrow cell cycle phases, as well as an increase of the granulocytic differentiation. The results suggest that leukocytosis and neutrophilia observed in this model of body fat increase are in fact a result of a complex modulation of the hematopoietic system.
19

Long-term Behavioral and Neuroendocrine Consequences of Early Adversity (Juvenile Stressor Exposure), and the Buffering Effects of ‘Comfort’ Food.

MacKay, Jennifer Christine January 2016 (has links)
The adolescent period has been proposed to be exquisitely sensitive to the impacts of stress and juvenile stressor exposure is associated with anxiety- and depressive- like characteristics in adulthood. Among adult rats, access to a palatable diet has shown to mitigate the effects of stressors, a form of ‘self-medication.’ The present collection of studies sought to further characterize the long-term consequences of stressor exposure early in the juvenile period, as well as the use of palatable food as a coping strategy. The first study (Chapter 2) highlighted the importance of methodological rigor in the design of experiments employing social stressors. The second study (Chapter 3) provided further evidence that exposure to juvenile social defeat can have long-lasting consequences into adulthood, and access to a palatable diet may impart some resilience to initial stressor exposure. The third study (Chapter 4) demonstrated that access to a palatable diet can mitigate the long-term behavioral consequences of a 3-day sub chronic non-social stressor applied during juvenility in pair housed rats. The fourth study (Chapter 5) sought to replicate these findings in individually housed (purportedly more stressed) animals. Interestingly, access to a palatable diet was sufficient to protect against the neuroendocrine consequences of juvenile stress but did not mitigate the behavioral consequences, raising the question of an effectiveness “threshold” of self-medication via a palatable diet. The final study (Chapter 6) provided some preliminary evidence that exposure to juvenile stress amid access to a palatable diet has long-lasting changes on dopamine receptor expression in the nucleus accumbens, although the functional significance needs further characterization. Collectively, all studies provided further evidence that self-medication with a palatable diet comes at the price of poor metabolic outcomes. The results of this body of work provide further evidence that exposure to stress during juvenility can have protracted effects into adulthood, at the cost of poor metabolic outcomes. It also raises the suggestion of an effectiveness threshold of palatable food to cope with stress. Further understanding of the interplay between stress and diet may serve to inform the development of prevention based programs to mitigate the rising tide of concurrent childhood obesity and levels of perceived stress.
20

Modulação de autofagia na prole de animais submetidos à dieta hiperlipídica na vida intrauterina, lactação e vida adulta / Autophagy modulation in the offspring from obese dams fed with high fat diet during pregnancy and lactation

Reginato, Andressa, 1990- 04 October 2015 (has links)
Orientador: Marciane Milanski Ferreira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Aplicadas / Made available in DSpace on 2018-08-27T16:06:12Z (GMT). No. of bitstreams: 1 Reginato_Andressa_M.pdf: 3622201 bytes, checksum: 6c4d49212fa7262052afb4aec8d81f48 (MD5) Previous issue date: 2015 / Resumo: O excesso na ingestão calórica e a obesidade têm afetado um número crescente de pessoas em diferentes países, sendo que a obesidade durante a gestação e lactação desempenha impacto negativo no fenótipo prole. Na vida adulta, a obesidade e a sobrecarga de lipídeos constituem fatores que resultam no comprometimento da autofagia, um processo de degradação lisossomal essencial para a manutenção da homeostase celular. A autofagia é responsável pela degradação e reciclagem de componentes citoplasmáticos como organelas senescentes, proteínas agregadas ou mal formadas, microrganismos invasores e macromoléculas. Apesar do conhecimento acerca do prejuízo na atividade autofágica no contexto da obesidade, alterações na homeostase deste processo na prole de mães obesas ainda não foram investigadas. Neste estudo, foi avaliada a hipótese de que a obesidade materna induzida por dieta hiperlipídica seria capaz de modular proteínas da via autofágica no hipotálamo e no fígado da prole de camundongos. Embora sem nenhuma alteração na atividade de autofagia no hipotálamo, a prole de mães obesas ao nascimento (d0) apresentou prejuízo nos marcadores de autofagia no fígado representado por aumento no conteúdo proteico de p62 e diminuição no conteúdo proteico de LC3-II. Ao desmame (d18), a prole de mães obesas teve comprometimento no conteúdo proteico dos marcadores de autofagia em ambos os tecidos (fígado e hipotálamo) quando comparados à prole de mães magras. Após o desmame, a prole de mãe controle e a prole de mãe obesa receberam dieta controle até a vida adulta (d82). Nessa condição não houve modulação dos marcadores de autofagia em nenhum dos tecidos avaliados, sendo que somente a reexposição à dieta hiperlipídica (dos 42 dias até 82 dias) foi responsável por alterar o conteúdo proteico dos marcadores de autofagia quando comparados aos animais com dieta hiperlipídica sem reexposição. Assim, parece que dieta hiperlipídica é essencial para a modulação negativa dos marcadores de autofagia na prole de mães obesas. Em conclusão, a prole de mãe obesa apresentou comprometimento precoce de marcadores de autofagia no fígado e no hipotálamo, o que poderia estar associado ao desenvolvimento de distúrbios metabólicos na prole na idade adulta / Abstract: The nutritional excess and obesity have affected a growing number of people in different countries, being that obesity during pregnancy and lactation has negative impact on offspring phenotype. In adulthood, obesity and lipids overload constitute factors that result in impairment of autophagy, a lysosomal degradation process essential for maintaining cellular homeostasis. Thus, autophagy is responsible for degradation and recycling of cytoplasmic components as senescent organelles, aggregated proteins or proteins poorly formed, microorganisms invaders and macromolecules. It is known that obesity and the use of high fat diet have a negative impact on cellular homeostasis. However, modulation of autophagy in the offspring of obese mothers has yet to be investigated. This study tested the hypothesis that maternal obesity induced by high fat diet would be able to modulate proteins of autophagy in the hypothalamus and liver of mice offspring. At birth (d0), the offspring exhibited prejudice in autophagy markers in liver and after weaning (d18) both tissues (liver and hypothalamus) had compromised autophagy markers. The animals receiving control diet after weaning until adulthood (d82) had no impairment of autophagy proteins in both tissues examined. However, when the animals were re-exposed to high-fat diet they had alteration in protein content of autophagy, when compared to animals with high fat diet without re-exposure. Thus, high fat diet seems to be essential for negative modulation of autophagy markers. In conclusion, the offspring of obese mothers presented early impairment of autophagy proteins in the liver and hypothalamus, which may be associated with the development of metabolic disorders in the offspring in adulthood / Mestrado / Metabolismo e Biologia Molecular / Mestra em Ciências da Nutrição e do Esporte e Metabolismo

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