Cell Metabolism
Volume 3, Issue 5, May 2006, Pages 321-331
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Article
The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis

https://doi.org/10.1016/j.cmet.2006.03.007Get rights and content
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Summary

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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