Identification and characterization of leucine responsive mRNAs in skeletal muscle of rats subjected to immobilization with large-scale sequencing

Abstract

Muscle atrophy is considered as an important factor for morbidity and mortality of patients. Thus, the development of strategies to improve muscle strength and to reduce symptoms of atrophy, are one of the biggest challenges in skeletal muscle research. Our laboratory has investigated the anti-catabolic effects of leucine involved in the control of skeletal muscle mass. Leucine, classified as a branched chain amino acid is as a potent pharmacological agent, preventing catabolism of muscular atrophy. Recent studies from our research group demonstrated that rats supplemented daily with leucine showed reduced weight loss of soleus muscle and also reduce the loss of cross-sectional area after 7 days of immobilization. This anti-atrophic effects of leucine was attributed to reduced gene expression of key components of the ubiquitin proteasome system, atrogin-1 and MuRF1. Moreover, it is possible that other factors and signaling pathways are involved in the anti-atrophic effect leucine. Therefore, the aim of this project is to conduct a prospective study, while using mRNA next-generation sequencing. Moreover, despite recent, large-scale sequencing is well established as a useful tool for identifying genes, pathways and responsive mechanisms, mainly because it can overcome the tracks normally resulting from the acquired knowledge in Cell and Molecular Biology. In this project, we intend to analyze the expression of Trib3 a pseudokinase known for acting in various cellular functions. In preliminary analyzes, we found that its expression was increased after three days of immobilization and reduced afterleucine supplementation. Accordingly, many studies have shown a link Trib3 with increased insulin resistance, and increases in expression of Trib3 after the consumption of a leucine-deficient diet. (AU)