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

The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis

  • Cell Metab. 2006 May;3(5):321-31. doi: 10.1016/j.cmet.2006.03.007.
Zhaoyu Li 1,  Luis B Agellon,  Theresa M Allen,  Masato Umeda,  Larry Jewell,  Andrew Mason,  Dennis E Vance
Affiliations

Affiliation

  • 1 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.
PMID: 16679290 DOI: 10.1016/j.cmet.2006.03.007
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.

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