The B-adrenergic pathway as a target in regulation of M1 and M2 polarization in type 2 diabetes

• Grant number: 23/07162-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: January 15, 2024
• End date: January 14, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: José Cesar Rosa Neto
• Grantee: Alexandre Abilio de Souza Teixeira
• Supervisor: Jonathan Peter Little
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of British Columbia, Okanagan (UBC), Canada
• Associated to the scholarship: 21/00352-0 - Effect of physical exercise throughout life on monocyte differentiation and function mechanisms and their relationship with the genes that control circadian rhythm, BP.PD

Abstract

Macrophages are immune cells present throughout the body that are essential for maintaining tissue homeostasis. Their remarkable plasticity allows them to acquire different phenotypes, capable of fighting infections (classically activated "M1-like" macrophages) or promoting tissue remodeling and repair (alternatively activated "M2-like" macrophages). These phenotypes are induced by different signals present in the microenvironment. Catecholamines (norepinephrine and epinephrine) activate adrenergic receptors expressed by macrophages and shape the effector functions of these cells in diverse contexts such as tissues or organs. The activation of different subsets of receptors seems to produce antagonistic effects, with ±-adrenergic receptors generally associated with pro-inflammatory functions and ²-adrenergic receptors (particularly ²2) related to inflammation resolution and tissue remodeling. However, little is known about ²1-adrenergic receptors. In our preliminary results, we observed that ²1-adrenergic receptor expression is increased while ²2-adrenergic receptor expression tends to decrease in M1 macrophages. Inflammatory processes, particularly those mediated by macrophages, are related to various pathologies such as the development and progression of insulin resistance and type 2 diabetes (T2D). There is a high prevalence of persons living with diabetes who also have cardiovascular diseases such as hypertension, which can impact diabetes treatment since these patients may receive medications that are ²-adrenergic pathway blockers, potentially increasing inflammatory response. Thus, ²-adrenergic receptors (²ARs) may play an important role in regulating macrophage function and the pathogenesis of T2D and its cardiovascular complications. Based on the information mentioned, our study aims to determine the role of ²-adrenergic receptors in the polarization, differentiation, function, and metabolism of macrophages under normal conditions and in T2D. (AU)