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

Abstract

+2Dedico este trabalho às pessoas mais importantes da minha vida, À toda minha famíliaQue soube compreender todos os momentos em que estive ausente, obrigada pelos constantes incentivos e torcida pelo meu futuro. Vocês são essenciais! Aos meus PaisSignificado de devoção e coragem, com o exemplo deles, aprendi que tudo é possível com força de vontade e pensamento positivo, e, sobretudo, a importância da dignidade e do caráter. Amor eterno! Ao meu marido, André, Pelo privilégio de ter você ao meu lado, sempre carinhoso, otimista e compreensivo até nos momentos mais difíceis. Pelos momentos de esperança que pensa, junto comigo, no nosso futuro. Amo você! Há três coisas fundamentais para a felicidade:alguma coisa para fazer, alguém para amar e algo para esperar. Joseph Addison AGRADECIMENTOS ESPE AGRADECIMENTOS ESPE AGRADECIMENTOS ESPE AGRADECIMENTOS ESPECIAIS CIAIS CIAIS CIAISAo meu orientador, Prof. Dr. Antonio Carlos Cicogna, pela oportunidade, credibilidade e por ter me ensinado que ciência não se faz em poucas horas, mas sim em investigação científica baseada na observação e experimentação, com perseverança e muita dedicação. ABSTRACTCurrently, 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 (Ca 2+ ) 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 Ca 2+ . 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 Ca 2+ 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.Obesi...

Obesity does not Lead to Imbalance Between Myocardial Phospholamban Phosphorylation and Dephosphorylation

“…Since the beta-adrenergic via is in charge of phosphorylation in the site of serum-16 of the PLB, we can infer that this system was not sufficiently stimulated to lead to changes in the myocardial PLB phosphorylation or that another system was opposed to such an activation. The behavior of pPLB-ser16 in this study is not in accordance with a previous study conducted in our laboratory 12 , in which decreased PLB was found in its phosphorylated state in serum 16 among obese rats treated with the same diet used in this study. We could not find an explanation for these different results; such a divergence could be related to the adiposity index in obese animals, which was 16% higher in the study conducted by Lima-Leopoldo 12 .…”

“…The behavior of pPLB-ser16 in this study is not in accordance with a previous study conducted in our laboratory 12 , in which decreased PLB was found in its phosphorylated state in serum 16 among obese rats treated with the same diet used in this study. We could not find an explanation for these different results; such a divergence could be related to the adiposity index in obese animals, which was 16% higher in the study conducted by Lima-Leopoldo 12 . No studies in literature analyzed the relationship between proteins that interfere in myocardial PLB phosphorylation and dephosphorylation in obese rats submitted to a hyperlipidic diet.…”

“…Relling et al 11 used obese rats for 12 weeks and showed increased PLB expression and decreased phosphorylated PLB (pPLB). Lima-Leopoldo 12 verified decreased pPLB via cAMP in serine 16 in obese rats for 15 weeks. These authors did not evaluate kinase and phosphatase proteins in the animals.…”