Regulation of GSK3-beta/Beta-catenin in skeletal muscle of rats supplemented with leucine and subjected to atrophy

Abstract

The process of muscle atrophy is highly organized and regulated, characterized by a reduced cross-sectional area of muscle fibers and protein content, strength reduction, increased fatigue and increased insulin resistance. Several pathways are considered important to the process of mass loss with concomitant proteolysis, such as the ubiquitin-proteasome. More recently has been shown the involvement of GSK3-² on gene expression of components of this proteolytic pathway. In our laboratory we have demonstrated that leucine, an essential amino acid and has the beginning of their metabolism in skeletal muscle, was able to strongly attenuate the gene expression of E3 ligases and the loss of muscle mass. Despite the clear protective effect of leucine, is not yet clear how this amino acid exerts this function. Considering these data, GSK3-² appears as a possible target, since this protein is essential for gene expression of atrogin-1 and MuRF1, two major E3 ligases in skeletal muscle tissue, as well as having an important role in metabolic integration. Thus, the aim of this project is to analyze the effect of leucine supplementation on muscle atrophy during GSK3-² (expression and activation) and ²-Catenin, the key transcription factor of this pathway.