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

Grant number: 16/12941-2
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): December 01, 2016
Effective date (End): November 30, 2019
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Anselmo Sigari Moriscot
Grantee:João Guilherme de Oliveira Silvestre
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/04090-0 - Identification and caracterization of mechanisms involved in skeletal muscle mass control and regeneration, AP.TEM
Associated scholarship(s):17/26819-7 - Role of TRB3 on skeletal muscle atrophy, BE.EP.PD


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)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
J.G. SILVESTRE; I.L. BAPTISTA; W.J. SILVA; A. CRUZ; M.T. SILVA; E.H. MIYABARA; S. LABEIT; A.S. MORISCOT. The E3 ligase MuRF2 plays a key role in the functional capacity of skeletal muscle fibroblasts. Brazilian Journal of Medical and Biological Research, v. 52, n. 9, . (12/13315-7, 15/04090-0, 16/12941-2)

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