Molecular and functional characterization of the effects of treatment with Tauroursodeoxycholic acid (TUDCA) on the skeletal muscles of mice subjected to protein restriction.

• Grant number: 25/02316-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Everardo Magalhães Carneiro
• Grantee: Julia Estevam dos Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Malnutrition, a serious global problem triggered by factors such as poverty and inequality, severely impacts health, manifesting itself in conditions such as marasmus and kwashiorkor. Kwashiorkor, characterized predominantly by protein deficiency associated with inadequate vitamin intake and increased carbohydrate intake, has an impact on the health and development of children, increasing their susceptibility to the development of chronic noncommunicable diseases (CNCDs) such as hypertension, type 2 diabetes mellitus (T2DM), obesity and even nonalcoholic fatty liver disease (NAFLD). Another striking consequence of protein malnutrition is the excessive loss of muscle mass. Skeletal muscle performs multiple crucial functions, since it is capable of contributing to basal energy expenditure and storing essential substrates, such as amino acids and glycogen, and is therefore important for maintaining the body's homeostasis. This loss of mass can occur due to interference of nutritional status in the protein synthesis and degradation pathway, where its decompensation results in decreased muscle weight and atrophy. Aiming to reverse these deleterious effects, we highlight the therapeutic actions of tauroursodeoxycholic acid, a bile acid that has already demonstrated effects in improving muscle function in models of obesity and aging. Our laboratory has already demonstrated that treatment with TUDCA is capable of reducing adiposity and ectopic fat deposition, improving glucose homeostasis and normalizing insulin secretion in obese rodents. However, little is known about the effects of TUDCA on skeletal muscle tissue in protein undernutrition. Therefore, the objective of this project is to evaluate the effects of TUDCA on functional and molecular alterations in the synthesis and degradation pathways of skeletal muscle in mice subjected to protein restriction. For this purpose, muscle strength will be evaluated in groups of mice, different types of skeletal muscle will be weighed, the protein content of the main proteins involved in protein synthesis signaling in the gastrocnemius muscle, p70S6K, 4EBP1, mTOR/pmTOR and AKT/p-AKT, p-ERK1/2 and ERK1/2, as well as the main proteins involved in protein degradation signaling in the gastrocnemius muscle will be evaluated through the analysis of the following proteolysis markers p-FOXO1 and FOXO1, p-Smad 2/3 and Smad 2/3, MURF1 and Atrogin, in samples from malnourished mice treated with TUDCA. This project should contribute to a better understanding of mechanisms that can mitigate the effects of malnutrition.