Figure 1. Metabolic reprogramming into M1 phenotype. Stimulation with LPS, INF-γ, or TNFα of macrophages favors a reprogramming toward the pro-inflammatory phenotype. One of the very first events is the TCA cycle halt resulting in the accumulation of citrate and succinate. The dysfunction of the TCA cycle activates a metabolic process known as the “Warburg effect.” The accumulation of succinate inhibits the succinate dehydrogenase (SDH) increasing the level of HIF-1α, a signaling molecule characteristic of the M1 phenotype. Inducible NO synthase, adenosine 5′-monophosphate-activated protein kinase (AMPK) pathway, ROS, and other pathways are also involved in this metabolic system. See text for details.