Polarization of M1 and M2 macrophages in individuals with low and high cardiorespiratory fitness: potential role of adipose tissue, aging and leptin

• Grant number: 21/11060-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): May 01, 2022
• Effective date (End): April 30, 2023
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Fábio Santos de Lira
• Grantee: Caíque de Figueiredo
• Supervisor: Jonathan Peter Little
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
• Research place: University of British Columbia, Okanagan (UBC), Canada
• Associated to the scholarship: 19/26378-6 - M1 and M2 macrophage polarization in individuals with low and high cardiorespiratory fitness: potential role of adipose tissue, aging and leptin, BP.DD

Abstract

Derived from a myeloid lineage in the bone marrow, monocytes are blood cells of the immune system that in tissues differentiate into macrophages with an anti-inflammatory (M2) or pro-inflammatory (M1) state. The polarization of macrophages to the inflammatory state in metabolic disorder, or repair in tissue and systemic homeostatic situations, is well established in the literature, showing that white adipose tissue deposits and physical fitness are important factors for maintaining the balance between phenotypes and, consequently, a healthy state. However, the macrophage response in individuals with different visceral fat thickness and levels of cardiorespiratory fitness, associated with the presence in vitro of leptin, secreted by adipose tissue and modulating pro-inflammatory pathways, deserves attention, mainly because leptin can also activate pathways of signaling related to the anti-inflammatory phenotype. This knowledge may be important to direct strategies to combat metabolic / inflammatory disorders caused, in part, by the imbalance of macrophage phenotypes in young and elderly people with low cardiorespiratory fitness and large visceral fat thickness. Thus, due to the high sensitivity of AMPK in detecting small changes in intracellular nucleotides, we hypothesize its role as a master regulator of the anti-inflammatory response of monocytes and macrophages. Furthermore, the second hypothesis of the present study is that lower concentrations of leptin found in eutrophic individuals or after physical exercise sessions, associated with the anti-inflammatory environment of individuals with high physical fitness, would be able to participate in the polarization of macrophages to the phenotype anti-inflammatory through the activation of AMPK. In this case, the increase in oxidative metabolism after AMPK activation via leptin (a similar action on skeletal muscle) would support the induction of the anti-inflammatory phenotype in macrophage polarization. Therefore, the primary objective of the present study is to examine the impact of visceral adipose tissue and leptin on macrophage polarization in young and elderly men with low and high cardiorespiratory fitness. (AU)