Fig. 2

Signaling pathways implicated in macrophage metabolic reprogramming. M1 macrophages are classically polarized by IFN-γ and LPS, and the activation of PI3K-AKT-mTOR-HIF-1α signaling cascade sustains glycolysis and PPP. In contrast, the activation of PPARs and AMPK signaling underpins FAO and mitochondrial activity in IL-4/IL-10 polarized M2 macrophages. Abbreviations: AKT, protein B; AMPK, adenosine 5'-monophosphate–activated protein kinase; ARG1, arginase 1; ERK, extracellular regulated protein kinases; FAO, fatty acid oxidation; GSK3β, glycogen synthase kinase-3 beta; HIF, hypoxia inducible factor; IFN-γ, interferon γ; IFNR, interferon receptor; IKK, inhibitor of kappa B kinase; IL, interleukin; IL-10R, interleukin-10 receptor; IL-4R, IL-4 receptor; LPS; lipopolysaccharide; MEK, mitogen-activated protein kinase kinase; MSR1, macrophage scavenger receptor 1; mTOR, mammalian target of rapamycin; mTORC1, mTOR complex 1; NF-κB, Nuclear factor-κB; OXPHOS, oxidative phosphorylation; PDK1, pyruvate dehydrogenase kinase isozyme 1; PGC1α, proliferator-activated receptor gamma coactivator 1 α; PI3K, phosphatidyl inositol 3-kinase; PKM2, pyruvate kinase 2; PPARγ, peroxisome proliferator activation receptor gamma; PPP, pentose phosphate pathway; Raf, rapidly accelerated fibrosarcoma; Ras, rat sarcoma; ROS, reactive oxygen species; TCA, tricarboxylic acid; TGF-β, trans-forming growth factor-β; TGFβR, TGF-β receptor; TLR, Toll-like receptor (Created with BioRender.com)