Multi-user Equipment approved in grant 24/20524-9: EchoMRI-3in1TM Whole Body Composition Analyzer.

• Grant number: 26/11553-0
• Support Opportunities: Multi-user Equipment Program
• Start date: August 01, 2026
• End date: July 31, 2033
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Adelino Sanchez Ramos da Silva
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Associated research grant: 24/20524-9 - Unraveling the Role of Rev-Erbalpha in Insulin Resistance in Skeletal Muscle: Molecular Mechanisms and Therapeutic Interventions., AP.TEM

Abstract

Obesity and insulin resistance in skeletal muscle (SM) are widely recognized as key determinants in the development of type 2 diabetes mellitus (T2DM) and other metabolic disorders. In this context, the Rev-Erb¿ protein, encoded by the nuclear receptor subfamily 1 group D member 1 (Nr1d1) gene, emerges as a promising molecular target for the treatment of insulin resistance due to its central role in regulating fundamental processes such as autophagy, mitochondrial biogenesis, inflammation, and the maintenance of skeletal muscle mass. Preliminary data from our thematic project (19/11820-5) support this hypothesis, demonstrating the relevance of Rev-Erb¿ in modulating these mechanisms. Therefore, the overall objective of this proposal is to investigate the role of the Nr1d1 gene in obesity- and T2DM-associated insulin resistance in SM using in vitro, in vivo, and in silico approaches in cellular, rodent, and human models. To this end, the following subprojects will be developed: 1) Effects of obesity and T2DM on Rev-Erb¿ and its relationships with insulin resistance; 2) Pharmacological and non-pharmacological interventions in circadian regulation and their association with insulin resistance; 3) Impact of Nr1d1 gene deletion in skeletal muscle on insulin resistance; 4) Effects of Rev-Erb¿ overexpression on insulin signaling in obesity and T2DM models; 5) Exploration of the role of Rev-Erb¿-regulated genes in modulating glucose uptake and insulin signaling pathways in C2C12 cells; 6) Identification of Rev-Erb¿ protein ligands through immunoprecipitation and mass spectrometry in muscle cells with and without insulin administration. The methodologies employed will include omics approaches such as RNA-seq, proteomics, and ATAC-seq, as well as traditional techniques like immunoblotting, RT-qPCR, interactome analysis, mass spectrometry, gene therapy (CRISPR/Cas9 and adeno-associated viral vectors), histology, immunohistochemistry, immunofluorescence, and bioinformatics. Statistical analysis will be conducted using parametric or non-parametric tests, depending on the data distribution. (AU)