Fig. 1

Metabolic rearrangement in macrophage polarization to proinflammatory or alternatively activated macrophages in vitro and in vivo. A In vitro, resting macrophages can be activated by various pathogen- or danger-associated molecular patterns (PAMPs or DAMPs), and cytokines polarize to classically activated proinflammatory M1 macrophages or alternatively activated anti-inflammatory M2 macrophages. B Upon in vivo tissue injury, damaged cell debris is released into the extracellular microenvironment, and an inflammatory response is mounted. Next, upon clearance of cell debris and DAMPs, the response changes to promote resolution of inflammation. Both in vitro (A left) and in vivo (B left), proinflammatory polarization has been associated with enhanced glycolytic metabolism; however, the majority of the related information has been elucidated in vitro. Both in vitro (A right) and in vivo (B right), increases in OXPHOS, FAO and glutaminolysis are associated with alternatively activated macrophages. Ac, Acetylation; CIII, complex III; Drp1, dynamin-related protein 1; Gln, Glutamine; Gpr18, G protein-coupled receptor 18; Me, Methylation; PRR, pattern recognition receptor; Pyr, Pyruvate; UCP2, mitochondrial uncoupling protein 2; ΔΨm, mitochondrial membrane potential. Solid lines: direct relationships; dashed lines: indirect relationships. Black circles: DAMPs; blue circles: anti-inflammatory cytokines; purple circles: proinflammatory cytokines; orange stars: ROS and RNS; black irregular ovals: phagocytosed particles