RESISTANCE TRAINING AS A STRATEGY TO MITIGATE METABOLIC DYSFUNCTION INDUCED BY MUSCLE-SPECIFIC DELETION OF ER¿

• Grant number: 25/16409-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: João Paulo Gabriel Camporez
• Grantee: João Pedro Bonfim Estanganeli
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Reduced estrogen activity, such as that which occurs during menopause, is associated with an increased risk of metabolic disorders, including insulin resistance and obesity. Estrogen signaling, mediated predominantly by its receptor alpha (ER¿) in skeletal muscle, plays a key role in maintaining energy homeostasis.Animal models with muscle-specific deletion of ER¿ confirm this importance, exhibiting a phenotype of increased adiposity, reduced insulin sensitivity, and muscle lipid accumulation. Despite the clear importance of ER¿, it remains an unresolved question whether non-pharmacological interventions, such as exercise training, can offset the deleterious effects of its absence. The present project aims to evaluate the potential of resistance training to mitigate the metabolic and structural impairments resulting from ER¿ deletion in skeletal muscle. To this end, female mice with muscle-specific deletion of ER¿ and their controls will be subjected to an eight-week resistance training protocol with progressive overload. The investigation will test the hypothesis that exercise can attenuate this adverse phenotype, evaluating the impact of training on glycemic homeostasis through glucose tolerance tests, on the molecular pathways of inflammation, on the pathways of protein synthesis and degradation in muscle and on the serum levels of markers of muscle damage.