The sea cucumber plasmalogen PlsEtn has been shown to be associated with various chronic diseases related to lipid metabolism. However, the mechanism is unclear. Therefore, the present study used the sea cucumber plasmanylcholine PakCho as a structural contrast to PlsEtn and assessed its effect in 8 week high-fat diet (HFD)-fed mice. The lipidomic approach based on high-resolution mass spectrometry combined with molecular biology techniques was used to evaluate the mechanism of PlsEtn. The results showed that both PlsEtn and PakCho significantly inhibited an increase in mouse body weight and liver total triglyceride and total cholesterol levels caused by HFD. In addition, oil red O staining demonstrated that lipid droplets stored in the liver were degraded. Meanwhile, untargeted lipidomic experiments revealed that total lipids (increased by 42.8 mmol/mg prot; p < 0.05), triglycerides (increased by 38.9 mmol/mg prot; p < 0.01), sphingolipids (increased by 1.5 mmol/mg prot; p < 0.0001), and phospholipids (increased by 2.5 mmol/mg prot; p < 0.05) were all significantly elevated under HFD. PlsEtn resolved lipid metabolism disorders by alleviating the abnormal expression of lipid subclasses. In addition, five lipid molecular species, PE (18:1/20:4), PE (18:1/20:3), PE (18:1/18:3), TG (16:0/16:0/17:0), and TG (15:0/16:0/18:1), were identified as the biomarkers of HFD-induced lipid metabolism disorders. Finally, lipophagy-associated protein expression analysis showed that HFD abnormally activated lipophagy via ULK1 phosphorylation and PlsEtn alleviated lipophagy disorder through lysosomal function promotion. In addition, PlsEtn performed better than PakCho. Taken together, the current study results unraveled the mechanism of PlsEtn in alleviating lipid metabolism disorder and offered a new theoretical foundation for the high-value development of sea cucumber.

中文翻译：

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海参缩醛磷脂通过自噬调节高脂饮食小鼠肝脏中的脂质分布

海参缩醛磷脂PlsEtn已被证明与多种与脂质代谢相关的慢性疾病有关。然而，其机制尚不清楚。因此，本研究使用海参血浆胆碱 PakCho 作为 PlsEtn 的结构对比，并评估其对 8 周高脂肪饮食 (HFD) 喂养的小鼠的效果。采用基于高分辨率质谱结合分子生物学技术的脂质组学方法来评估 PlsEtn 的机制。结果显示，PlsEtn和PakCho均显着抑制HFD引起的小鼠体重以及肝脏总甘油三酯和总胆固醇水平的增加。此外，油红O染色表明储存在肝脏中的脂滴被降解。同时，非靶向脂质组学实验显示，总脂质（增加了 42.8 mmol/mg prot；p < 0.05）、甘油三酯（增加了 38.9 mmol/mg prot；p < 0.01）、鞘脂（增加了 1.5 mmol/mg prot；p < 0.01）。 0.0001）和磷脂（增加 2.5 mmol/mg 蛋白质；p < 0.05）在 HFD 下均显着升高。 PlsEtn 通过减轻脂质亚类的异常表达来解决脂质代谢紊乱。另外，还有五种脂质分子，PE(18:1/20:4)、PE(18:1/20:3)、PE(18:1/18:3)、TG(16:0/16:0) /17:0) 和 TG (15:0/16:0/18:1) 被确定为 HFD 诱导的脂质代谢紊乱的生物标志物。最后，自噬相关蛋白表达分析表明，HFD 通过 ULK1 磷酸化异常激活自噬，PlsEtn 通过促进溶酶体功能缓解自噬紊乱。此外，PlsEtn 的表现优于 PakCho。综上所述，本研究结果揭示了PlsEtn缓解脂质代谢紊乱的作用机制，为海参的高值化开发提供了新的理论基础。