Role of TRB3 on skeletal muscle atrophy

• Grant number: 17/26819-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 01, 2018
• End date: April 30, 2019
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Anselmo Sigari Moriscot
• Grantee: João Guilherme de Oliveira Silvestre
• Supervisor: Ho-Jin Koh
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: 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)

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)

NASCIMENTO ALVES, PAULA KETILLY; SILVESTRE, JOAO G.; DAMASCENA SOUGEY, WENDDY WYLLIE; CRUZ, ANDRE; MORISCOT, ANSELMO SIGARI. Improved Electrical Stimulation-Based Exercise Model to Induce Mice Tibialis Anterior Muscle Hypertrophy and Function. APPLIED SCIENCES-BASEL, v. 12, n. 15, p. 14-pg., 2022-08-01. (18/24418-8, 16/12941-2, 21/05827-7, 18/24419-4, 15/04090-0, 17/09398-8, 21/03066-9, 17/26819-7)