Vassiliou Evros, Farias-Pereira Renalison
Department of Biological Sciences, Kean University, Union, NJ 07083, USA.
Department of Plant Biology, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
Int J Mol Sci. 2023 Jul 27;24(15):12032. doi: 10.3390/ijms241512032.
Macrophage polarization is influenced by lipids, which also exert significant control over macrophage functions. Lipids and their metabolites are players in intricate signaling pathways that modulate macrophages' responses to pathogens, phagocytosis, ferroptosis, and inflammation. This review focuses on lipid metabolism and macrophage functions and addresses potential molecular targets for the treatment of macrophage-related diseases. While lipogenesis is crucial for lipid accumulation and phagocytosis in M1 macrophages, M2 macrophages likely rely on fatty acid β-oxidation to utilize fatty acids as their primary energy source. Cholesterol metabolism, regulated by factors such as SREBPs, PPARs, and LXRs, is associated with the cholesterol efflux capacity and the formation of foam cells (M2-like macrophages). Foam cells, which are targets for atherosclerosis, are associated with an increase in inflammatory cytokines. Lipolysis and fatty acid uptake markers, such as CD36, also contribute to the production of cytokines. Enhancing the immune system through the inhibition of lipid-metabolism-related factors can potentially serve as a targeted approach against tumor cells. Cyclooxygenase inhibitors, which block the conversion of arachidonic acid into various inflammatory mediators, influence macrophage polarization and have generated attention in cancer research.
巨噬细胞极化受脂质影响，脂质对巨噬细胞功能也具有重要调控作用。脂质及其代谢产物参与复杂的信号通路，调节巨噬细胞对病原体的反应、吞噬作用、铁死亡和炎症。本综述聚焦于脂质代谢与巨噬细胞功能，并探讨治疗巨噬细胞相关疾病的潜在分子靶点。虽然脂肪生成对于M1巨噬细胞中的脂质积累和吞噬作用至关重要，但M2巨噬细胞可能依赖脂肪酸β-氧化将脂肪酸作为其主要能量来源。由固醇调节元件结合蛋白（SREBPs）、过氧化物酶体增殖物激活受体（PPARs）和肝X受体（LXRs）等因子调控的胆固醇代谢，与胆固醇流出能力和泡沫细胞（M2样巨噬细胞）的形成有关。作为动脉粥样硬化靶点的泡沫细胞与炎性细胞因子增加有关。脂解作用和脂肪酸摄取标志物，如CD36，也有助于细胞因子的产生。通过抑制脂质代谢相关因子来增强免疫系统，可能成为针对肿瘤细胞的靶向方法。环氧化酶抑制剂可阻断花生四烯酸转化为各种炎性介质，影响巨噬细胞极化，已在癌症研究中引起关注。
