The characterization of Rev-Erb-alpha on different metabolic conditions: from mice to humans

• Grant number: 22/16162-9
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: January 04, 2024
• End date: December 23, 2024
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Ana Paula Pinto
• Supervisor: Sarah J. Lessard
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 21/08693-1 - Effect of global or conditional deletion (skeletal muscle) of the Nr1d1 gene on aging, BP.PD

Abstract

Recently it was demonstrated that the nuclear receptor Rev-erb±, codified by the Nr1d1 gene, plays an important role in the skeletal muscle, regulating exercise capacity and atrophy-related genes. It was shown that this molecule is highly sensitive to endurance chronic training, but until the present moment, few data are available about Rev-erb± responses in skeletal muscle to resistance exercise model. Another important discovery was that obesity inhibited Nr1d1 expression Also, Nr1d1 was downregulated in skeletal muscle samples of aged mice, suggesting that Rev-erb± is a strong candidate for the dysregulation of aging factors. Therefore, the main aim of this project is to investigate the role of Rev-erb± in response to resistance exercise, endurance exercise, high-fat diet, and aging in mice and human samples. The tibialis anterior (TA) of 8-week-old ICR mice and the TA and adipose tissue of CD-1 mice will be used for molecular analysis of Real-Time quantitative PCR, and western blotting. The cellular model will use the human skeletal muscle cell line, and cells knocked down with siRNA to silence the coding gene of Rev-erb±. After, the cells will be submitted to in vitro mechanical stretch mimicking strength exercise muscle contraction. For this model, it will be performed in vitro protein synthesis, Real-Time quantitative PCR, and western blotting,For human samples, the vastus lateralis muscle of younger and older healthy men will be used for the molecular analysis of mRNA levels and protein. An unpaired test-t or two-way analysis of variance (ANOVA) will be used to examine the differences between the experimental groups. All statistical analyses will be two-sided, and the significance level will be set at p-0.05. (AU)