Mitochondrial Metabolism of Human Adipose Tissue Macrophages: How physical activity delays immune system ageing

• Grant number: 25/06336-8
• Support Opportunities: Scholarships abroad - Research
• Start date: December 15, 2025
• End date: July 29, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Fábio Santos de Lira
• Grantee: Fábio Santos de Lira
• Host Investigator: Paulo Jorge Gouveia Simoes da Silva Oliveira
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
• Institution abroad: Centro De Neurociências E Biologia Celular, Portugal

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 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 energy metabolism of monocytes/macrophages and adipose tissue macrophages, favoring polarization towards anti-inflammatory phenotypes. The aim of the present study is to explore the impact of the physical activity levels on macrophage polarization (both infiltrated in adipose tissue and monocytes/macrophages) with normal weight and/or overweight/obese subjects. The study will be divided into two stages: 1) individuals undergoing programs for health and food/nutrition literacy and physical activity, with healthcare centers and their control group aged between 18 and 60 years will be recruited; 2) individuals aged between 18 and 60 years will be recruited and undergo central obesity assessments using ultrasound of the abdominal region, classified into LowVAT (¿3.1 cm) and HighVAT (¿5.1 cm), and an adjusting for physical activity levels will be conducted. 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). Furthermore, glucose uptake and energetic 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. 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. (AU)