Estudo da bioenergética mitocondrial de cardiomiócitos de camundongos obesos

• Autor(a) principal: Bernardo, Amélia Faustino
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12732
• topic: Bioenergetics; Obesity; Mitochondrial dysfunction; Bioenergética; Obesidade; Disfunção mitocondrial; CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA ENDOCRINA

Obesity is a chronic disease resulting from the excess of fat in the body. The increase of obesity in the world has been on the clinical and epidemiological phenomenon of the present. Population studies and animal models, show that the origin of the "obesity epidemic", is related to genetic factors and habits acquired during early and adult life, such as changes in dietary habits and reduction in physical activity. In this context, nutritional changes during the period of lactation play an important role in the development of obesity, type 2 Diabetes Mellitus and cardiovascular diseases. Mitochondria are the central coordinators of energy metabolism, playing a role in the survival and function of the cardiomyocytes due to high energy demand of the myocardium. Functional and structural alterations of this organelle have been associated with metabolic disorders as well to myocardium dysfunction, and consequent progression of cardiomyopathies. In this study, we evaluated the bioenergetics and the ultrastructure of cardiomyocytes from obese (OG) and control (CG) mice overfed during lactation. The oxygen consumption of cardiac fibers was assessed by high resolution respirometry, using a 2K-oxigraph-Oroboros. The ultrastructure of the cardiomyocytes was analyzed by transmission electron microscopy, and the content of proteins carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 2 (UCP2), glucose transporter 1 and 4, (GLUT1) and (GLUT4), activated Protein kinase by AMP (AMPK) and AMP-activated protein kinase phosphorylated (pAMPK) was assessed by Western Blotting (WB). In addition, animal body mass, retroperitoneal and epididymal fat, and fasting blood glucose were determined. Our results confirmed that animals in group OG, at 90 days of life, showed an increase in body mass and mediastinun and retroperitoneal fat when compared with CG. Respiratory rates were similar in both groups when we used complexes I and II substrates. However, when palmitoil-L-carnitine fatty acid was used, the maximum respiratory rate of OG was significantly lower than CG. The ultrastructural analysis of the cardiomyocytes of OG showed intense damage in mitochondrial matrix and greater presence of lipid droplets, characterizing ectopic deposition. WB analyses showed a significant increase of CPT1 and UCP2 contents in OG compared to CG. There were no significant differences in GLUT1 content between groups; however, we observed a greater content of GLUT4 in OG. In addition, we found a higher content of AMPK in OG, while the content of pAMPK was similar between groups. However, the pAMPK/AMPK ratio was significantly lower in OG. These results suggest that overfeeding during lactation leads to obesity in adult life with changes in bioenergetics and ultrastructure of cardiomyocytes.