O EFEITO DO EXERCÍCIO NAS ALTERAÇÕES EPIGENÉTICAS DO PGC1 :O IMPACTO NO DIABETES MELLITUS TIPO 2

Coordenadora: SANDRA APARECIDA BENITE RIBEIRO

The world prevalence diabetes type 2 is increasing and intramuscular accumulation of fatty acid metabolites is gradually more recognized as core features of this condition as lipotoxicity induces insulin resistance. Emerging evidence suggests that defects in mitochondria, key organelle on lipid metabolism, play a central role on insulin resistance. Mitochondria homeostasis is tightly regulated by a nucleus?mitochondria signaling pathway and peroxisome proliferator-activated receptor γ coactivator-1α (PGC1) is the master regulator of important mitochondria process. PGC1 is downregulated in insulin resistant skeletal muscle and abnormal posttranslational modification at histone, epigenetic modifications, is rising as an important factor. Studies have demonstrated the benefits of regular exercise on improving insulin sensitivity however the mechanism for this outcome is not entirely identify. Therefore the submitted project aims to verify the effect aerobic exercise on epigenetic modification of PGC1 and on mitochondria function in type 2 diabetic animals. For that Wistars rats will be induced to type 2 diabetes by the combination of a small dose of streptozotocin and high caloric diet. Age matched non-diabetic will be used as control. After the diabetic induction protocol half animals will perform 6 weeks of aerobic exercise, swimming, and the other half will be keep in rest condition. At the end blood and gatrocnemius muscle will be collected and insulin resistance by the HOMA, histone modification at PGC1 promoter, mitochondria biogenesis number and function, and glucose transporter (GLUT4) will be assessed. We are expecting that type 2 diabetes animals will present decrease in histone acetylation (Ac-H3K9) and increase in histone methylation (H3K9-3me) at PGC1 promoter representing repression of this gene. In addition we believe that diabetic will induce subnormal mitochondria biogenesis, function and number, and GLUT4 expression. Furthermore we are expecting that exercise will attenuate the effect of diabetes on PGC1 promoter and that can reverse diabetic effect on mitochondria and GLUT4 and improve insulin resistance. This project will be carried out at Department of Physiology at Federal University of Goiás during 2014 to 2015. We are confident that the results of will contribute to the understanding of the mechanism underlying the development of diabetes and of the benefic effects of aerobic exercise as a treatment for this alarming disease.