Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affair), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, PR China.
Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affair), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, PR China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, 266003, Qingdao, Shandong, PR China.
Fish Shellfish Immunol. 2022 Jul;126:12-20. doi: 10.1016/j.fsi.2022.05.003. Epub 2022 May 5.
LPCAT3, a subtype of lysophosphatidylcholine acyltransferases, is a key enzyme in phosphatidylcholine remodeling pathway and plays a significant role in mediating inflammatory response in mammals. However, its inflammatory function in fish has yet to be discovered. Herein, this study aimed to investigate its role in inflammation in Larimichthys crocea. We analyzed the coding sequence of Larimichthys crocea LPCAT3 (Lc-LPCAT3) and explored the effect of Lc-LPCAT3 on palmitate (PA)-induced inflammation. We found that in macrophage cell line of Larimichthys crocea, the mRNA expression of Lc-lpcat3 was upregulated by PA with the elevated pro-inflammatory genes expression, including il1β, il6, il8, tnfα and ifnγ. Next, the role of Lc-LPCAT3 in inflammation induced by PA was further investigated. Results showed that knockdown of Lc-LPCAT3 mitigated PA-induced pro-inflammatory genes mRNA expression, including il1β, il8, tnfα and ifnγ, in which JNK signaling pathway was involved. In contrast, overexpression of Lc-LPCAT3 induced pro-inflammatory genes expression including il1β, tnfα and ifnγ. Furthermore, several transcription factors with negative regulation of Lc-LPCAT3 promoter activity were discovered including LXRα, RXRα, PPARα, PPARγ, CEBPα, CEBPβ, CEBPδ, SREBP1 and SREBP2, and SREBP1 had the strongest regulatory effect. In conclusion, we first discovered that fish LPCAT3 participated in PA-induced inflammation, and targeting SREBP1 might be an effective coping strategy.
LPCAT3 是溶血磷脂酰胆碱酰基转移酶的一种亚型，是磷脂酰胆碱重塑途径中的关键酶，在哺乳动物炎症反应中发挥重要作用。然而，其在鱼类中的炎症功能尚未被发现。本研究旨在探讨其在大黄鱼炎症反应中的作用。我们分析了大黄鱼 LPCAT3（Lc-LPCAT3）的编码序列，并探讨了 Lc-LPCAT3 对棕榈酸（PA）诱导炎症的影响。我们发现，在大黄鱼巨噬细胞系中，PA 可上调 Lc-lpcat3 的 mRNA 表达，同时上调促炎基因的表达，包括 il1β、il6、il8、tnfα 和 ifnγ。接下来，我们进一步研究了 Lc-LPCAT3 在 PA 诱导炎症中的作用。结果表明，Lc-LPCAT3 的敲低减轻了 PA 诱导的促炎基因 mRNA 表达，包括 il1β、il8、tnfα 和 ifnγ，其中涉及 JNK 信号通路。相反，Lc-LPCAT3 的过表达诱导了包括 il1β、tnfα 和 ifnγ 在内的促炎基因的表达。此外，还发现了几种转录因子可负调控 Lc-LPCAT3 启动子活性，包括 LXRα、RXRα、PPARα、PPARγ、CEBPα、CEBPβ、CEBPδ、SREBP1 和 SREBP2，其中 SREBP1 具有最强的调控作用。总之，我们首次发现鱼类 LPCAT3 参与了 PA 诱导的炎症反应，靶向 SREBP1 可能是一种有效的应对策略。
