College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong Province, China; School of Food Science and Technology, Jiangnan University, 1800, Lihu Road, 214122, Wuxi, Jiangsu Province, China.
College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong Province, China.
Redox Biol. 2021 Jul;43:102002. doi: 10.1016/j.redox.2021.102002. Epub 2021 May 7.
Emerging evidence suggests that the reduction of ethanolamine plasmalogen (PlsEtn) is associated with in Alzheimer's disease and metabolic diseases. However, the mechanistic bases for PlsEtn on the these diseases are not well understood. Plasmalogens are primarily synthesized in the liver and enriched in brain. To this end, the present study sought to investigate the potential role of PlsEtn on steatohepatitis and memory impairments and its underlying mechanism. Here we show that peroxisome dysfunction and impairment of PlsEtn synthesis pathway occurs in both of hippocampus and liver, resulting in the decrease of PlsEtn level in APP/PS1 mice and HFD-fed mice. shGNPAT induced PlsEtn deficiency in hepatocytes induces p75NTR enhancement leading to decreased lipolysis activity, thereby exacerbating steatosis. Moreover, in the brain, PlsEtn administration appears to not only improve steatosis but also prevent Alzheimer's disease through restoration of TrkA/p75NTR balance. Together, our findings reveal a molecular mechanistic insight into the preventive role of plasmalogen modulation against steatosis and memory impairments via p75NTR inhibition.
新出现的证据表明，乙醇胺磷脂（PlsEtn）的减少与阿尔茨海默病和代谢疾病有关。然而，PlsEtn 对这些疾病的机制基础还不是很清楚。磷脂主要在肝脏中合成，并在大脑中富集。为此，本研究旨在探讨 PlsEtn 对肝脂肪变性和记忆障碍的潜在作用及其潜在机制。在这里，我们表明，过氧化物酶体功能障碍和 PlsEtn 合成途径受损发生在海马体和肝脏中，导致 APP/PS1 小鼠和高脂肪饮食喂养小鼠中 PlsEtn 水平降低。shGNPAT 在肝细胞中诱导 PlsEtn 缺乏会增强 p75NTR，导致脂肪分解活性降低，从而加重脂肪变性。此外，在大脑中，PlsEtn 的给药似乎不仅可以改善脂肪变性，而且可以通过恢复 TrkA/p75NTR 平衡来预防阿尔茨海默病。总之，我们的研究结果揭示了一种分子机制，即通过抑制 p75NTR，调节磷脂对脂肪变性和记忆障碍的预防作用。
