FIG. 4.

Immunometabolic differences between M2 and M1 macrophages. Both M1 and M2 macrophages can produce energy by glucose metabolism. M2 macrophages use OXPHOS and the TCA cycle, similarly to quiescent macrophages, but additionally demonstrate increased FFA uptake and oxidation (FAO) to supplement the TCA cycle and their energy needs. M1 macrophages increase glucose uptake and produce energy via oxidative glycolysis, resulting in lactate production. In addition, they exhibit a broken TCA cycle leading to the accumulation of both citrate and succinate. Succinate accumulation leads proinflammatory cytokine IL-1β release via HIF-1α. α-KG, alpha-ketoglutarate; FAO, fatty acid oxidation; HIF-1α, hypoxia-inducible factor-1α; NADPH, nicotinamide adenine dinucleotide phosphate; TCA, tricarboxylic acid. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars