Fig. 2

Part of metabolic adaptations of macrophages. Macrophage activation through LPS/IFN-γ results in similar flux distribution patterns towards glycolysis regardless of the pathway activated. HIF-1α activation can increase fructose-2,6-bisphosphate concentration and the glycolytic flux. CARKL could antagonize LPS-induced cytokines production. The decrease of OXPHOS induced by LPS leads to the accumulation of intermediate metabolites in the tricarboxylic acid cycle, especially succinic acid. Succinic acid can transfer from mitochondria to intracellular, inhibit the activity of prolyl hydroxylase (PHD) enzyme, and increase HIF-1α by promoting its stability. Notably, mTOR-HIF-1α axis involves in glycolysis in M1-polarized macrophages. In hypoxia state, HIF-1α can promote glycolysis by inducing expression of the related enzymes and transcriptional effectors. Meanwhile, HIF-1α can promote the expression of proinflammatory genes in macrophages