Impact of Aromatase Inhibitors Combined with Exogenous Androgen Use on Insulin Sensitivity and Energy Metabolism

• Grant number: 25/07069-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• 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: Felipe Garcia da Silva Sucupira
• Supervisor: Gerald Shulman
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Yale School of Medicine (YSM), United States
• Associated to the scholarship: 23/16186-8 - Impact of Testosterone on Insulin Sensitivity and Energy Metabolism in Male Mice, BP.DR

Abstract

Lifestyle and increased consumption of high-fat diet largely contribute to the development of obesity, insulin resistance, type 2 diabetes (DM2) and cardiovascular disease. One of the consequences of this lifestyle and high-fat diet is Non-Alcoholic Fatty Liver Disease (NAFLD), which affects about 30% of adults and up to 10% of children in developed countries. In addition, obesity is the main cause of low testosterone concentrations in men, affecting approximately 20% to 40% of men with obesity according to epidemiological studies, which contrasts with the prevalence of 4% to 5% in the male population. in general. Low testosterone concentrations in men have profound health implications, including obesity, reduced skeletal muscle mass, type 2 diabetes, erectile dysfunction and decreased quality of life. Several mechanisms are currently considered to cause insulin resistance, such as abnormal lipid metabolism and ectopic accumulation, mitochondrial dysfunction, inflammation and endoplasmic reticulum stress. As the liver and skeletal muscle tissue are central organs in the control of glycemic homeostasis and insulin action, the general objective of this project is to study (in vivo) the effects of androgen hormone replacement on global energy metabolism and lipid deposition. This project will allow the evaluation of the impact of sex hormone signaling, such as testosterone and dihydrotestosterone, on energy metabolism, in addition to the mechanisms involved in the development of NAFLD, DM2 and obesity, thus promoting possible new targets and approaches for the development of treatment/prevention of the metabolic syndrome. (AU)