美国加州大学圣迭戈Joseph L. Witztum、Xiaoli Sun等研究人员合作发现，氧化磷脂的中和可改善非酒精性脂肪性肝炎。该研究于2019年11月21日在线发表于国际一流学术期刊《细胞—代谢》。

研究人员表示，由于氧化应激而产生的氧化磷脂（OxPL）具有促炎性和促动脉粥样硬化作用，但它们在非酒精性脂肪性肝炎（NASH）中的作用尚不清楚。

研究人员发现，OxPL在人和小鼠的NASH中积累。使用表达E06的功能性单链可变片段（中和OxPL的天然抗体）的转基因小鼠，研究人员证明了OxPL在NASH中的因果作用。在高脂血症Ldlr-/-小鼠中靶向OxPL可改善NASH的多个方面，包括脂肪变性、炎症、纤维化、肝细胞死亡以及进展为肝细胞癌。

从机理上讲，研究人员发现OxPL促进ROS积累，诱导肝细胞线粒体功能障碍。在AMLN饮食喂养的Ldlr-/-小鼠中中和OxPL可以降低氧化应激，改善肝脏和脂肪组织线粒体功能，以及脂肪酸氧化。 这些结果表明靶向OxPLs可能是NASH的有效治疗策略。

附：英文原文

Title: Neutralization of Oxidized Phospholipids Ameliorates Non-alcoholic Steatohepatitis

Author: Xiaoli Sun, Jason S. Seidman, Peng Zhao, Ty D. Troutman, Nathanael J. Spann, Xuchu Que, Fangli Zhou, Zhongji Liao, Martina Pasillas, Xiaohong Yang, Jason A. Magida, Tatiana Kisseleva, David A. Brenner, Michael Downes, Ronald M. Evans, Alan R. Saltiel, Sotirios Tsimikas, Christopher K. Glass, Joseph L. Witztum

Issue&Volume: November 21, 2019

Abstract: Oxidized phospholipids (OxPLs), which arise due to oxidative stress, are proinflammatoryand proatherogenic, but their roles in non-alcoholic steatohepatitis (NASH) are unknown.Here, we show that OxPLs accumulate in human and mouse NASH. Using a transgenic mousethat expresses a functional single-chain variable fragment of E06, a natural antibodythat neutralizes OxPLs, we demonstrate the causal role of OxPLs in NASH. TargetingOxPLs in hyperlipidemic Ldlr/ mice improved multiple aspects of NASH, including steatosis, inflammation, fibrosis,hepatocyte death, and progression to hepatocellular carcinoma. Mechanistically, wefound that OxPLs promote ROS accumulation to induce mitochondrial dysfunction in hepatocytes.Neutralizing OxPLs in AMLN-diet-fed Ldlr/ mice reduced oxidative stress, improved hepatic and adipose-tissue mitochondrialfunction, and fatty-acid oxidation. These results suggest targeting OxPLs may be aneffective therapeutic strategy for NASH.

DOI: 10.1016/j.cmet.2019.10.014

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30605-9