Abstract 14116: Exercise and Specialized Proresolving Lipid Mediators Stimulate Mitochondrial Metabolism in Macrophages

Abstract

Exercise may prevent the development and progression of chronic inflammatory diseases through alterations in immune cell function. We find that macrophages isolated from mice subjected to 4 weeks of voluntary wheel exercise display enhanced basal and maximal mitochondrial respiration. We have previously shown that exercise also increases the production of specialized proresolving mediators (SPMs), macrophage phagocytosis, and resolution of acute inflammation; however, whether exercise-induced SPM formation directly alters macrophage metabolism remains unknown. SPMs stimulate resolution through actions on specific G-protein coupled receptors (GPCRs) in macrophages ( e.g. , RvD1=> Fpr2). Therefore, we treated macrophages for 1 h with SPMs that act through distinct GPCRs ( e.g. , RvD1, RvD2, RvE1, and MaR1) and found enhanced basal (vehicle vs 1nM SPM; 6.11±0.1 vs RvD1 7.76±0.6 vs RvD2 9.48±0.9 vs RvE1 7.20±0.5 vs MaR1 8.73±0.9 pmol/min/μg protein; P<0.05; n =3), maximal (vehicle vs 0.1nM SPM; 9.06±1.1 vs RvD1 14.37±1.1 vs RvD2 16.54±2.7 vs RvE1 12.32±1.5 vs MaR1 13.28±1.3 pmol/min/μg protein; P<0.05; n =3), and ATP-linked respiration (vehicle vs 1nM SPM; 2.83±0.2 vs RvD1 4.50±0.3 vs RvD2 4.39±0.2 vs RvE1 4.71±0.3 vs MaR1 4.20±0.2 pmol/min/μg protein; P<0.05; n =3). Stimulation of mitochondrial metabolism with RvD1 was receptor mediated as Fpr2 -deficient macrophages displayed no significant changes in mitochondrial respiration following treatment (vehicle vs 1nM RvD1; basal 6.74±0.6 vs 6.52±0.2; maximal 11.54±1.2 vs 13.26±1.0; ATP-linked 5.84±0.8 vs 5.33±0.2 pmol/min/μg protein). Collectively, these data suggest that exercise-induced production of SPMs stimulates mitochondrial metabolism in macrophages, which could underlie their common proresolving properties and the exercise-induced amelioration of chronic inflammatory diseases.