@article{a6b52d8f7ddf4dffb36f850497ba0b34,
title = "The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis",
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.",
keywords = "HUMDISEASE",
author = "Zhaoyu Li and Agellon, {Luis B.} and Allen, {Theresa M.} and Masato Umeda and Larry Jewell and Andrew Mason and Vance, {Dennis E.}",
note = "Funding Information: We thank Sandra Ungarian, Susanne Lingrell, Audric Moses, Priscilla Gao, Elaine Moase, Randal Nelson, and Dorothy Rutkowski for excellent technical assistance. We thank Dr. William Garver, University of Arizona, for providing colloidal silica and techniques for plasma membrane purification. We thank Dr. Mark Lee, University of Alberta, for help in preparations of slides of liver sections and useful comments. We thank Dr. Vince Bain and Dr. Donna Douglas, University of Alberta, for providing human liver samples. We thank Dr. Jean Vance and Dr. Yang Zhao for helpful discussions. This research was supported by grants from the Canadian Institutes of Health Research (CIHR). Z. Li is a CIHR/HSFC (Heart and Stroke Foundation of Canada) Strategic Training Fellow in Stroke, Cardiovascular, Obesity, Lipid, Atherosclerosis Research (SCOLAR) supported by a grant from Astra Zeneca. D. Vance holds the Canada Research Chair in Molecular and Cell Biology of Lipids and is a Scientist of the Alberta Heritage Foundation for Medical Research.",
year = "2006",
month = may,
doi = "10.1016/j.cmet.2006.03.007",
language = "English (US)",
volume = "3",
pages = "321--331",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",
}