磷脂酰胆碱与磷脂酰乙醇胺的比例会影响膜的完整性和脂肪性肝炎。

The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis.

作者信息

Li Zhaoyu, Agellon Luis B, Allen Theresa M, Umeda Masato, Jewell Larry, Mason Andrew, Vance Dennis E

机构信息

Department of Biochemistry and Canadian Institutes of Health Research Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2 Canada.

出版信息

Cell Metab. 2006 May;3(5):321-31. doi: 10.1016/j.cmet.2006.03.007.

DOI:10.1016/j.cmet.2006.03.007

PMID:16679290

Abstract

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are major phospholipids in mammalian membranes. In liver, PC is synthesized via the choline pathway or by methylation of PE via phosphatidylethanolamine N-methyltransferase (PEMT). Pemt(-/-) mice fed a choline-deficient (CD) diet develop rapid steatohepatitis leading to liver failure. Steatosis is observed in CD mice that lack both PEMT and multiple drug-resistant protein 2 (MDR2), required for PC secretion into bile. We demonstrate that liver failure in CD-Pemt(-/-) mice is due to loss of membrane integrity caused by a decreased PC/PE ratio. The CD-Mdr2(-/-)/Pemt(-/-) mice escape liver failure by maintaining a normal PC/PE ratio. Manipulation of PC/PE levels suggests that this ratio is a key regulator of cell membrane integrity and plays a role in the progression of steatosis into steatohepatitis. The results have clinical implications as patients with nonalcoholic steatohepatitis have a decreased ratio of PC to PE compared to control livers.

摘要

磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）是哺乳动物细胞膜中的主要磷脂。在肝脏中，PC通过胆碱途径合成，或通过磷脂酰乙醇胺N-甲基转移酶（PEMT）对PE进行甲基化来合成。喂食胆碱缺乏（CD）饮食的Pemt（-/-）小鼠会迅速发展为脂肪性肝炎，导致肝功能衰竭。在缺乏PEMT和多药耐药蛋白2（MDR2，PC分泌到胆汁中所必需的）的CD小鼠中观察到脂肪变性。我们证明，CD-Pemt（-/-）小鼠的肝功能衰竭是由于PC/PE比值降低导致膜完整性丧失所致。CD-Mdr2（-/-）/Pemt（-/-）小鼠通过维持正常的PC/PE比值避免了肝功能衰竭。对PC/PE水平的调控表明，该比值是细胞膜完整性的关键调节因子，并在脂肪变性发展为脂肪性肝炎的过程中起作用。这些结果具有临床意义，因为与对照肝脏相比，非酒精性脂肪性肝炎患者的PC与PE比值降低。