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Role of TRB3 on skeletal muscle atrophy

Grant number: 17/26819-7
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): May 01, 2018
Effective date (End): April 30, 2019
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal researcher:Anselmo Sigari Moriscot
Grantee:João Guilherme de Oliveira Silvestre
Supervisor abroad: Ho-Jin Koh
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of South Carolina, United States  
Associated to the scholarship:16/12941-2 - Identification and characterization of leucine responsive mRNAs in skeletal muscle of rats subjected to immobilization with large-scale sequencing, BP.PD

Abstract

Muscle atrophy is well-thought-out as an important element for mortality and morbidity of patients. Thus, the development of approaches to reduce symptoms of atrophy and to improve muscle strength are one of the biggest defies in skeletal muscle research area. Our laboratory has investigated the anti-catabolic effects of leucine related with the control of skeletal muscle mass. Leucine (a branched chain amino acid) is known as a potent pharmacological agent, inhibiting catabolism of skeletal muscle and we have showed that daily supplementation of leucine reduced the weight loss of soleus muscle and also reduced the loss of cross-sectional area after 7 days of immobilization. These anti-atrophic effects of leucine were attributed to reduced atrogin-1 and MuRF1 gene expression, key components of the ubiquitin proteasome system. However, other factors and signaling pathways may be involved in the anti-atrophic effect leucine. The IGF-1/PI3K/Akt pathway is known to play a key role in skeletal muscle mass regulation by Akt phosphorylation, that inducing mTOR to activate protein synthesis through S6K1 and 4EB1. Studies has shown that TRB3 negatively regulates Akt by directing binding and TRB3 is well described as a potential regulator of insulin signaling in multiple tissues. However, roles of TRB3 in skeletal muscle mass regulation are note fully understood. In this project, we intend to analyze the expression of TRB3 during atrophic process and after leucine supplementation, analyzing its effects on skeletal muscle mass regulation. In preliminary analyzes, we found that its expression was increased after three days of immobilization and reduced after leucine supplementation. (AU)

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