Dissertation Hellen Chaves Barbosa

AUTHOR: Hellen Chaves Barbosa

TITLE: Epigenetic modifications of histones and oxidative stress in skeletal muscle: type 2 diabetes versus physical exercise

ADVISOR:  Profa. Dra. Sandra Aparecida Benite Ribeiro and Prof. Dr. Hanstter Hallison Alves Rezende

DEFENSE DATE: 02/26/2021

ABSTRACT

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disease which is highly prevalent in today's populations. It has several epigenetic which are a result of the environment influencing several processes in the regulation of metabolic pathways and its development as well. Homeostasis and mitochondrial biogenesis are quite important factors in the regulation of lipid metabolism epigenetic modifications in skeletal muscle mitochondria. They have been pointed out as the responsible mechanisms for the development of T2DM. Moreover, physical exercise affects several metabolic pathways which function to improve metabolic deregulation of T2DM, so that mitochondria are candidates for such beneficial effects on the regulation of lipid metabolism. Thus, in this study we present the epigenetic mechanisms underlying the biogenesis and mitochondrial homeostasis regulators in the skeletal muscle. Furthermore, the study focuses on the epigenetic modifications of histones and the possible mechanisms of physical exercise in the improvement of the T2DM. The study was based on a systematic review PRISMA of the epigenetic mechanisms of changes in the histones which are responsible for the T2DM and the effect of physical exercise on these changes. We concluded that exercise promotes improvements in cellular metabolism through reducing oxidative stress and increasing the expression of peroxisome proliferator-activated receptor γ coactivator-1α r (PGC1), respiratory nuclear factors 1(NRF1), mitochondrial transcription factor (TFAM) and myocyte enhancer factor-2 (MEF2) upstream through acetylation of histones (H3K36ac and H3K27ac) and trimethylation (H3K4me3). Such factor positively regulates the cascade of mitochondrial biogenesis, which improves energy metabolismo and glucose homeostasis. However, there are still few studies focused on the effect of chronic physical exercise on epigenetic modifications caused by T2DM.