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

Grant number: 13/19387-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2014
Effective date (End): December 31, 2014
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Anselmo Sigari Moriscot
Grantee:Mirella Ribeiro Bento
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


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.

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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)
CRUZ, ANDRE; FERIAN, ANDREA; ALVES, PAULA K. N.; SILVA, WILLIAM JOSE; BENTO, MIRELLA RIBEIRO; GASCH, ALEXANDER; LABEIT, SIEGFRIED; MORISCOT, ANSELMO SIGARI. Skeletal Muscle Anti-Atrophic Effects of Leucine Involve Myostatin Inhibition. DNA AND CELL BIOLOGY, v. 39, n. 12, . (12/22488-2, 13/19387-2, 15/04090-0, 17/09398-8, 18/24419-4)

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