Choline deficiency-induced liver damage is reversible in Pemt(-/-) mice.
Hepatic tissue has two pathways for phosphatidylcholine (PC) synthesis, i.e., the cytidinediphosphocholine (CDP-choline) pathway and the methylation pathway, which utilizes phosphatidylethanolamine-N-methyltransferase (PEMT). Fatal liver damage occurs in Pemt(-/-)mice fed a choline-deficient (CD) diet. We investigated whether liver damage can be reversed by the addition of dietary choline. Mice (8 wk old) were fed the CD purified diet for 4 d, a choline-supplemented (CS) diet (CD diet + 0.4% choline chloride) for 4 d, or the CD diet for 3 d and a CS diet for 1 d (CD/CS). Pemt(-/-)mice fed the CD diet for 3 d exhibited liver damage as assayed by plasma aminotransferase levels. The livers appeared normal after subsequent feeding of the CS diet for 1 d (CD/CS). The activities of plasma aminotransferases of CD/CS fed mice were comparable to Pemt(-/-)mice fed the CS diet. Hepatic PC and triacylglycerol levels as well as plasma PC levels in the CD/CS-fed Pemt(-/-)mice were lower than those of mice fed the CD diet and began to approach normal levels. Although the CD diet induces liver damage in Pemt(-/-)mice, this damage can be rapidly reversed by the addition of dietary choline.
Waite
Kristin A
KA
Department of Biochemistry and CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
Cabilio
Nora R
NR
Vance
Dennis E
DE
D000818:Animals; D002794:Choline / Q000008:administration & dosage*; D002796:Choline Deficiency / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010713:Phosphatidylcholines / Q000096:biosynthesis* / Q000097:blood; D050918:Phosphatidylethanolamine N-Methyltransferase; D000637:Transaminases / Q000097:blood / Q000378:metabolism
D010713:Phosphatidylcholines; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D000637:Transaminases; D002794:Choline