The role of macrophage mitochondrial dynamics in the regulation of browning.

• Grant number: 21/00187-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2023
• Effective date (End): February 28, 2025
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Pedro Manoel Mendes de Moraes Vieira
• Grantee: Marcelo Rodrigues Berçot
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 20/16030-0 - Immunometabolic adaptation of tissue resident macrophages in health and disease, AP.TEM

Abstract

Adipose tissue can be divided into three major types: white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue (BeAT). BAT and BeAT generate heat by oxidizing fatty acids, while white adipocytes handle fat storage. Adaptative thermogenesis (Adaptative thermogenesis) produces heat through brown and beige adipocytes. During cold exposure BAT increases UCP1 expression, enhancing heat production. UCP1 dissociates the proton-electrochemical gradient, uncoupling the electron transport chain from complex V, and protons pumped to the intermembrane space return to the mitochondrial matrix via UCP1, generating heat. Different immune cells reside in BAT, and macrophages play a critical role in maintaining Adaptative thermogenesis homeostasis. BAT oxidizes mainly glucose and lipids to produce heat, and during adaptative thermogenesis, BAT microenvironmental cues changes, inflecting in macrophages metabolism and polarization, which are intimately connected to macrophages mitochondrial fission (regulated by DRP1) and fusion (regulated by Mitofusin 1/2 (Mfn1/2)) process. Since changes in macrophages mitochondrial dynamics could disrupt macrophages function and tissue homeostasis, we hypothesized that modulation of macrophages mitochondrial dynamics would impact macrophage metabolic adaptation in response to cold stress, impacting UCP1 expression and the subsequent Adaptative thermogenesis. From a translational perspective, if accumulated energy can be used and dissipated in heat by brown/beige adipose tissue, we will have an alternative to reduce excess weight in obesity.