Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, Shandong, People's Republic of China.
Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, Shandong, People's Republic of China.
FASEB J. 2024 Nov 30;38(22):e70180. doi: 10.1096/fj.202401279RR.
Phosphatidylethanolamine (PE) is a ubiquitous bioactive lipid in cells, which participates in regulating many metabolic processes. Exogenous PE has been reported to play a positive regulatory role in macrophage inflammatory responses. However, the molecular mechanisms of PE in regulating macrophage inflammation are not completely understood. In the present study, transcriptomic analysis of PE-stimulated macrophages of large yellow croaker revealed that differentially expressed genes were mainly active in cellular components of the mitochondrial respiratory chain, which corresponded to the significant enrichment of the oxidative phosphorylation pathway. Consistent with this result, PE significantly increased ATP content and protein expression of NDUFB3 (mitochondrial respiratory chain complex I subunit) in macrophages. Meanwhile, transcriptomic data showed that PE treatment downregulated the transcript levels of nlrp3 and upregulated the transcript levels of suppressor of cytokine signaling 3 (socs3), suggesting that PE may alleviate macrophage inflammation by interfering with the activation of NLRP3 inflammasome. Further analysis showed that PE significantly attenuated dietary PA-mediated macrophage inflammation via NLRP3-Caspase-1 in vitro and in vivo. Given that PE abundance is strongly correlated with mitochondrial function, the present study hypothesized that PE-mediated inflammatory modulation may be attributed to the positive effects on mitochondrial function. As expected, PE significantly ameliorated PA-induced mitochondrial dysfunction and reduced intracellular reactive oxygen species production and malondialdehyde content in macrophages, indicating that the improvement of mitochondrial function is an important mechanism involved in the positive effect of PE on PA-induced inflammation. In conclusion, this study elucidates the critical role of mitochondrial function in PE-mediated regulation of inflammation in macrophages, which expands the understanding of the regulatory mechanisms of phospholipid metabolism on dietary fatty acid-induced inflammation. This study may provide new intervention targets and nutritional regulation strategies for improving chronic inflammatory diseases.
磷脂酰乙醇胺（PE）是细胞中一种普遍存在的生物活性脂质，参与调节许多代谢过程。已有报道称，外源性 PE 在巨噬细胞炎症反应中发挥正向调节作用。然而，PE 调节巨噬细胞炎症的分子机制尚不完全清楚。在本研究中，通过对大黄鱼巨噬细胞进行 PE 刺激的转录组分析，发现差异表达基因主要活跃于线粒体呼吸链的细胞成分中，这与氧化磷酸化途径的显著富集相对应。与这一结果一致的是，PE 显著增加了巨噬细胞中的 ATP 含量和 NDUFB3（线粒体呼吸链复合物 I 亚基）的蛋白表达。同时，转录组数据显示，PE 处理下调了 nlrp3 的转录水平，上调了细胞因子信号转导抑制因子 3（SOCS3）的转录水平，表明 PE 可能通过干扰 NLRP3 炎性小体的激活来减轻巨噬细胞炎症。进一步分析表明，PE 通过 NLRP3-Caspase-1 在体外和体内显著减轻了 PA 介导的巨噬细胞炎症。鉴于 PE 丰度与线粒体功能密切相关，本研究假设 PE 介导的炎症调节可能归因于对线粒体功能的积极影响。正如预期的那样，PE 显著改善了 PA 诱导的线粒体功能障碍，并减少了巨噬细胞内的活性氧产生和丙二醛含量，表明改善线粒体功能是 PE 对 PA 诱导的炎症产生积极影响的重要机制。总之，本研究阐明了线粒体功能在 PE 调节巨噬细胞炎症中的关键作用，扩展了对磷脂代谢对膳食脂肪酸诱导的炎症的调节机制的认识。本研究可为改善慢性炎症性疾病提供新的干预靶点和营养调控策略。
