Energetic sensors and polarization of monocytes / macrophages M1 and M2: potential influence of visceral adipose tissue and aerobic fitness

Abstract

Monocytes are blood cells of the immune system, when infiltrating tissues are distinguished in macrophages M1 or M2, linked to a pro or anti-inflammatory activity, respectively. The M1 phenotype is predominant in white adipose tissue (TAB) of obese subjects, it participates directly in the release of proinflammatory cytokines during the process of chronic inflammation of low grade and exhibits predominance of glycolytic metabolism. On the other hand, M2 phenotype is mostly found in the BAT of eutrophic individuals, secretes cytokines that mediate the anti-inflammatory response, presents oxidative metabolism and its polarization is marked by the practice of physical exercise. Thus, equilibrium between M1 and M2 is essential for homeostatic maintenance of cells. However, increased visceral fat deposits and low aerobic fitness are determining factors for the M1 phenotype. Circulating concentrations of glucose and fatty acids modulate different intracellular energy sensors, as well as activate and / or inhibit the synthesis of different hormones involved in energy homeostasis. An important energy sensor for detecting oscillations in cellular glucose concentrations is AMP-activated protein kinase (AMPK). On the other hand, an important hormone involved in the remodeling of adipose tissue is leptin. Leptin is a hormone released mainly by BAD that has central and peripheral functions, among them, regulation of appetite, energy expenditure and modulation of the immune response. In monocytes, this hormone is able to stimulate the activation, proliferation and secretion of these cells. However, the response of monocytes to polarization stimuli for the M1 or M2 phenotype, in the absence or presence of leptin in eutrophic and obese individuals, mainly with excess visceral fat, with different levels of physical conditioning (low or high oxygen consumption maximum) is incipient. Given the issues raised, in the present project we will explore the following questions: 1) how body composition and aerobic fitness influence the differentiation of monocytes to macrophages of M1 or M2 phenotype in vitro; 2) role of leptin in the polarization of macrophages of M1 or M2 phenotype in vitro according to body composition and aerobic fitness. (AU)