Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke.
Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke.
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DOI：
10.1016/j.celrep.2023.112617
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发表时间：
2023-06
期刊：
影响因子：
8.8
通讯作者：
Lei Li;Shu-qi Cheng;Yu-qin Sun;Jianbing Yu;Xin-xin Huang;Yin-feng Dong;J. Ji;Xi-Yue Zhang
中科院分区：
文献类型：
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作者：
Lei Li;Shu-qi Cheng;Yu-qin Sun;Jianbing Yu;Xin-xin Huang;Yin-feng Dong;J. Ji;Xi-Yue Zhang
神经元聚集和清除是影响急性缺血性脑卒中神经炎症损伤的重要因素。新出现的证据表明，能量代谢是必不可少的小胶质细胞的功能，特别是小胶质细胞的吞噬作用，这决定了脑损伤的程度。在这里，我们证明了Resolvin D1（RvD 1），一种来自二十二碳六烯酸（DHA）的脂质介质，促进了小胶质细胞对中性粒细胞的吞噬作用，从而减少了中性粒细胞在大脑中的积累，减轻了缺血性大脑中的神经炎症。进一步的研究表明，RvD 1重新编程能量代谢，从糖酵解到氧化磷酸化（OXPHOS），为小胶质细胞吞噬提供足够的能量。此外，RvD 1增强小胶质细胞谷氨酰胺摄取，并刺激β-氨基分解，以支持OXPHOS，从而促进ATP的产生，这取决于腺苷5′-单磷酸（AMP）激活的蛋白激酶（AMPK）的激活。总的来说，我们的研究结果表明，RvD 1重新编程能量代谢，促进小胶质细胞吞噬中性粒细胞缺血性中风后。这些研究结果可能指导中风治疗的观点，从调节小胶质细胞免疫代谢。
Neutrophil aggregation and clearance are important factors affecting neuroinflammatory injury during acute ischemic stroke. Emerging evidence suggests that energy metabolism is essential for microglial functions, especially microglial phagocytosis, which determines the degree of brain injury. Here, we demonstrate that Resolvin D1 (RvD1), a lipid mediator derived from docosahexaenic acid (DHA), promotes the phagocytosis of neutrophils by microglia, thereby reducing neutrophil accumulation in the brain and alleviating neuroinflammation in the ischemic brain. Further studies reveal that RvD1 reprograms energy metabolism from glycolysis to oxidative phosphorylation (OXPHOS), providing sufficient energy for microglial phagocytosis. Moreover, RvD1 enhances microglial glutamine uptake and stimulates glutaminolysis to support OXPHOS to boost ATP production depending on adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activation. Overall, our results reveal that RvD1 reprograms energy metabolism to promote the microglial phagocytosis of neutrophils after ischemic stroke. These findings may guide perspectives for stroke therapy from modulating microglial immunometabolism.