Modulation of Amino Acids metabolism in Muscle and Adipose Tissue: Effects of Physical Exercise and Bariatric Gastric Bypass Surgery.

Abstract

Recent studies indicate a strong correlation among plasmatic levels of branched-chain amino acids (BCAA) and its metabolites with insulin resistance (IR) in humans. Regarding animal models, data suggest that increased BCAA levels can contribute in the reduction of insulin sensitivity. In parallel, over the last 20 years after the propagation of gastric bypass bariatric surgery (GBS) there has been a great progress in the treatment of obesity morbidity and also diabetes. It is important to mention that such improvement in insulin resistance can precede the weight loss thus indicating other mechanism for the improved glucose metabolism. In this context, a recent study which compared GSB and caloric restriction effects in the management of diabetes, despite both treatments had achieved the similar weight loss, had demonstrated that only GBS lowered BCAAs levels. However, the mechanisms by which the reduction of BCAA levels can improve insulin sensitivity are still poorly understood. Another important treatment of IR and obesity is physical exercise. Previous studies from our group demonstrated such effect insulin sensitivity in chronic and also in acute exercise protocols. Nevertheless, these studies have focused only in inflammatory aspects of IR. In this project, we will study the high-fat diet effects on BCAA metabolism by analyzing its circulating levels, oxidative enzymes and transporter expression in animal model. We will also see BCAA levels in obese subjects before and after the GBS, and then after they will be associated with tissue levels of BCATm, mTOR, JNK e IRS-1Ser312. Lastly, we will assess the influence aerobic exercise (chronic and acute) on these parameters in obese animals.