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

314 Scopus citations

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 1 2006

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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