Crosstalk between innate immune cells and thermogenic adipocytes in the regulation of energetic metabolism

• Grant number: 21/08330-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2021
• End date: August 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Paulo Henrique de Melo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

The mammals are euthermic species, capable of adapting to different ambient temperatures maintaining body temperature stable through the regulation mechanism. The adaptive thermogenesis has been widely studied not only as a form of adaptation of mammals to the cold, additionally this process adaptive leads to increased energy expenditure and greater uptake of circulating macronutrients. Brown Adipose Tissue (BAT) is the greater responsible for substrate clearance and increased energy expenditure during adaptative thermogenesis and it has been considered a therapeutic target key to the treatment of Obesity and Type 2 Diabetes. Interactions of immune cells and adipocytes have been shown during adaptive thermogenesis supporting the metabolic and thermal regulation process. Among different innate immune cells, eosinophils have been implicated in this process, being mainly associated with the recruitment process of thermogenic adipocytes to white fat deposits. However, the biological relevance, as well as the mechanisms involved in these interactions between adipocyte and eosinophils have not yet been identified. It seems eosinophils act on fat deposition by secreting factors that can stimulate activation of these adipocytes. Our research group has been working intensively in the identification and characterization of oxidized lipid species (oxylipins) withaction on the thermogenesis of brown and/or beige adipocytes. Lipidomic experiments performed in BAT of mice exposed to cold showed increased concentration of lipids that are products of the oxidative activity of 5- lipoxignase (5-LOX) after 7 days of exposure to temperature of 5C. BAT has several cell types, including many immune cells, we have questioned which cell type would be responsible for the production of these lipids in the adipose tissues. Surprisingly we have found that eosinophils were the only cells that expressed significant amount of 5-LOX in the BAT. Taken together, we hypothesize that eosinophils play a role of support to brown adipocytes during the process of adaptive thermogenesis bysecreting lipids with the ability to promote thermogenesis, insulin sensitivity and/or macronutrient uptake. Here we aim: 1) to understand the interaction mechanisms between eosinophils and thermogenic adipocytes during adaptive thermogenesis; 2) identify the oxylipins involved in this process and; 3) test the hypothesis that 5-LOX expressed in eosinophils plays a critical role in this process. (AU)