The role of CYP2E1 and interacting proteins in the regulation of thermogenesis in brown adipose tissue.

• Grant number: 23/16397-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: May 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Licio Augusto Velloso
• Grantee: Gabriely Amanda Cremasco
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Obesity is a serious global health issue, impacting millions of adults and children. Linked to chronic diseases such as type 2 diabetes and cancer, obesity results from an imbalance in the energy balance, involving the complex interaction between caloric intake and energy expenditure. Despite advances in understanding mechanisms, therapeutic options are limited, emphasizing the need for innovative strategies. The energy balance is regulated by four main components, including caloric intake and energy expenditure related to physical activity. Endogenous factors such as hormones influence appetite regulation and thermogenesis. Thermogenesis, crucial for body weight, is mediated by brown adipose tissue (BAT), specialized in generating heat. Proteins like UCP1, TRAF2, and PRDM16 play key roles in BAT activation. The project aims to investigate the enzyme CYP2E1 and its protein interactions, suggesting its involvement in thermoregulation. The hypothesis is that CYP2E1 influences BAT response to cold, justified by the incomplete understanding of thermogenesis mechanics. Objectives include evaluating CYP2E1 expression and associated proteins in BAT of mice exposed to different thermal conditions. The experimental protocol involves exposing mice to varied temperatures, followed by molecular analysis of adipose tissue. RNA extraction, followed by real-time PCR, will be used to assess gene expression. The C57BL/6 animal model will undergo different thermal protocols, with euthanasia at the end of each exposure. Genes CYB5A, PDX1, AASDH, and FDX2 were identified as functional interactors of CYP2E1, considered potential therapeutic targets for obesity. The study justification lies in the opportunity to identify new therapeutic targets for obesity treatment, given the partial understanding of thermogenesis mechanics. The methodology involves molecular techniques such as RNA extraction, real-time PCR, and statistical analysis to assess BAT changes in response to various thermal exposures.