The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis

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

Research output: Contribution to journalArticle

273 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)321-331
Number of pages11
JournalCell Metabolism
Volume3
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

Fingerprint

Fatty Liver
Phosphatidylcholines
Choline
Membranes
Liver Failure
Phosphatidylethanolamine N-Methyltransferase
Liver
phosphatidylethanolamine
Bile
Methylation
Phospholipids
Cell Membrane
Diet
Pharmaceutical Preparations
Proteins

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. / Li, Zhaoyu; Agellon, Luis B.; Allen, Theresa M.; Umeda, Masato; Jewell, Larry; Mason, Andrew; Vance, Dennis E.

In: Cell Metabolism, Vol. 3, No. 5, 05.2006, p. 321-331.

Research output: Contribution to journalArticle

Li, Zhaoyu ; Agellon, Luis B. ; Allen, Theresa M. ; Umeda, Masato ; Jewell, Larry ; Mason, Andrew ; Vance, Dennis E. / The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. In: Cell Metabolism. 2006 ; Vol. 3, No. 5. pp. 321-331.
@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.}",
year = "2006",
month = "5",
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",

}

TY - JOUR

T1 - The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis

AU - Li, Zhaoyu

AU - Agellon, Luis B.

AU - Allen, Theresa M.

AU - Umeda, Masato

AU - Jewell, Larry

AU - Mason, Andrew

AU - Vance, Dennis E.

PY - 2006/5

Y1 - 2006/5

N2 - 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.

AB - 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.

KW - HUMDISEASE

UR - http://www.scopus.com/inward/record.url?scp=33646121972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646121972&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2006.03.007

DO - 10.1016/j.cmet.2006.03.007

M3 - Article

C2 - 16679290

AN - SCOPUS:33646121972

VL - 3

SP - 321

EP - 331

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 5

ER -