Effects of MTCH2 muscle-specific gene deletion on apoptotic, lipogenic, oxidative, insulin and inflammatory pathways in the muscle of lean and obese animals submitted to short-term aerobic exercise

• Grant number: 20/08398-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2022
• Status: Discontinued
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Leandro Pereira de Moura
• Grantee: Vivian Cristina da Cruz Rodrigues
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated scholarship(s): 24/05621-8 - Long-term effects of MTCH2 knockdown by AAV8 of mice on a high-fat diet, BE.EP.DR

Abstract

Obesity contributes to the development of muscle mitochondriopathy. This condition impairs lipid metabolism and disrupts apoptotic activity in these cells. Animals that overexpress the protein mitochondrial carrier homolog 2 (MTCH2) have greater accumulation of body fat, elevated mitochondrial dysfunction and hyperglycemia. On the other hand, animals that had MTCH2 deletion in muscle tissue were protected from weight gain and hyperinsulinemia. In addition, these animals showed improvement in mass and mitochondrial function, which triggered an enhancement in aerobic performance and cardiac function. In this context, understanding the mechanism of action of MTCH2 becomes extremely important. Nevertheless, the role of physical exercise in reducing body weight, improving mitochondrial functionality and reducing hyperglycemia is well known. However, it is not yet known whether these beneficial effects of physical exercise are due to some modulation of MTCH2 caused by this practice. Therefore, the aim of the present proposal will be to investigate how different aerobic exercise protocols (acute, short term and chronic) act in the modulation of MTCH2 protein in skeletal muscle of obese animals. After the end of the exercise protocols, physiological tests to assess the metabolic health of the animals will be performed. Then, blood and muscle tissues (gastrocnemius and soleus) will be collected for further genetic and biomolecular analysis, and mitochondrial isolation. The following signaling pathways will be assessed in muscle tissues: insulin, inflammatory, apoptotic, lipogenic, lipolytic and oxidative phosphorylation. At the end of the present study, if our hypothesis is confirmed, we could list MTCH2 as a protein that is sensitive to physical exercise, and also, we will be able to elucidate at which time physical exercise is capable and more efficient to control its expression.