Papel da irisina na polarização de macrófagos em camundongos submetidos à dieta hiperlipídica

Abstract

In obese individuals, the chronic low-grade inflammatory process shows constant polarization of classically activated macrophages (M1) in the adipose tissue. Irisin has anti-inflammatory and antidiabetogenic properties and it may be a modulator of inflammation observed in obesity. Our aim was to evaluate the effects of irisin on macrophage polarization in mouse subjected to high fat diet. C57Bl/6 male mice were randomly divided in control (C) and high fat diet (HF) groups and mantained in the respective diet for 30 weeks. Bone marrow derived cells were then extracted and differentiated into naive macrophages (M0), that were then incubated with 20 nM, 50 nM of irisin, LPS+IFN-γ (to induce M1 macrophages) or IL-4 (to induced M2 macrophages). Macrophage phenotype was evaluated by flow cytometry through CD206 and CD301 expression. Nitrite and reactive oxygen species (ROS) production, phagocytic capacity, cell viability and arginase-1 expression were also analyzed. On both C and HL animals, IL-4 and both irisin doses were able to increase F480⁺CD206⁺ cells number, however without alteration in F480⁺CD301⁺ cells number and arginase-1 expression. Irisin was not able to induce nitrite and ROS production or to modulate phagocytosis and cell viability. Irisin was able to elicit an IL-4- induced M2-like profile in macrophages in animals subjected to high fat diet, suggesting an anti-inflammatory action of this cytokine with potential therapeutic use in obesity control.