POTENTIAL ROLE OF THE BETA-ADRENERGIC PATHWAY ON ENERGY METABOLISM OF CD14+ MONOCYTES: CHARACTERIZATION OF M1 AND M2 HALLMARKERS

• Grant number: 23/11489-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2025
• End date: December 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Fábio Santos de Lira
• Grantee: Tiago Olean Oliveira
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil

Abstract

The association between sedentary behavior, physical inactivity and high caloric intake favors the accumulation of fat in the central region, increasing the risk of developing non-communicable chronic diseases. In addition, this condition affects the neuro-immune axis, impacting macrophage ²-adrenergic signaling, and mitochondrial metabolism, favoring polarization toward a persistent inflammatory state. On the other hand, improvement in cardiorespiratory fitness (CRF) and reduction of body fat through physical training can promote positive modulations in the AR-²2 pathway in the energy metabolism of macrophages, favoring polarization towards anti-inflammatory phenotypes. The present study aims to explore the impact of the ²2-adrenergic pathway on macrophage polarization in clinical and non-clinical conditions. The study will be divided into two stages: 1) individuals undergoing treatment with chronic ²-blockers and their peers aged between 18 and 59 years will be recruited; 2) i ndividuals aged between 18 and 40 years will be recruited and undergo central obesity assessments using ultrasound of the abdominal region, classified into LowVAT (d3.1 cm) and HighVAT (e5.1 cm). Blood samples will be collected to determine the metabolic and inflammatory profile, flow cytometry (CD14++CD16-, CD14++ CD16+ and CD14+ CD16++), LPS-stimulated whole blood culture (cytokine production) and mRNA (AMPK, PGC-1±, TFAM, NF-ºB, AR-²2, MFN1 and 2, FIS1 and MT-ATP6) will be evaluates. Furthermore, glucose uptake and metabolism of CD14+ monocytes will be analyzed using the colorimetric kit and Seahorse XF to evaluate glycolytic and oxidative metabolism. Isolated monocytes CD14+ will be evaluating polarization of macrophages (M1 and M2) will be examined in the presence or absence of ²2-adrenergic pathway activators. Data will be presented as mean and standard deviation, and the Student's t-test or Mann-Whitney test will be used to compare groups. Adjusted comparisons will be performed using two-way analysis of covariance or generalized linear models and associations will be tested using linear regressions.