Facultad de Odontología, Instituto de Investigación de Ciencias Odontológicas, Universidad de Chile, Santiago, Chile.
Facultad de Ciencias Químicas y Farmacéuticas and Facultad de Medicina, Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile.
Front Immunol. 2020 Jan 10;10:2993. doi: 10.3389/fimmu.2019.02993. eCollection 2019.
Macrophage activation is intimately linked to metabolic reprogramming. Inflammatory (M1) macrophages are able to sustain inflammatory responses and to kill pathogens, mostly by relying on aerobic glycolysis and fatty acid biosynthesis. Glycolysis is a fast way of producing ATP, and fatty acids serve as precursors for the synthesis of inflammatory mediators. On the opposite side, anti-inflammatory (M2) macrophages mediate the resolution of inflammation and tissue repair, switching their metabolism to fatty acid oxidation and oxidative phosphorylation. Over the years, this classical view has been challenged by recent discoveries pointing to a more complex metabolic network during macrophage activation. Lipid metabolism plays a critical role in the activation of both M1 and M2 macrophages. Recent evidence shows that fatty acid oxidation is also essential for inflammasome activation in M1 macrophages, and glycolysis is now known to fuel fatty acid oxidation in M2 macrophages. Ultimately, targeting lipid metabolism in macrophages can improve the outcome of metabolic diseases. Here, we review the main aspects of macrophage immunometabolism from the perspective of the metabolism of lipids. Building a reliable metabolic network during macrophage activation will bring us closer to targeting macrophages for improving human health.
巨噬细胞的激活与代谢重编程密切相关。炎症（M1）巨噬细胞能够维持炎症反应并杀死病原体，主要依赖于有氧糖酵解和脂肪酸生物合成。糖酵解是产生 ATP 的快速途径，脂肪酸则作为炎症介质合成的前体。相反，抗炎（M2）巨噬细胞介导炎症的消退和组织修复，将其代谢转换为脂肪酸氧化和氧化磷酸化。多年来，这一经典观点受到了最近发现的挑战，这些发现指出在巨噬细胞激活过程中存在更为复杂的代谢网络。脂代谢在 M1 和 M2 巨噬细胞的激活中起着关键作用。最近的证据表明，脂肪酸氧化对于 M1 巨噬细胞中的炎性小体激活也是必不可少的，而糖酵解现在已知可以为 M2 巨噬细胞中的脂肪酸氧化提供燃料。最终，靶向巨噬细胞中的脂代谢可以改善代谢性疾病的预后。在这里，我们从脂质代谢的角度综述了巨噬细胞免疫代谢的主要方面。在巨噬细胞激活过程中构建一个可靠的代谢网络，将使我们更接近于通过靶向巨噬细胞来改善人类健康。
