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Choline Deficiency–Induced Liver Damage Is Reversible in Pemt−/− Mice

2002; Elsevier BV; Volume: 132; Issue: 1 Linguagem: Inglês

10.1093/jn/132.1.68

1541-6100

Kristin Waite, Nora R. Cabilio, Dennis E. Vance,

Amino Acid Enzymes and Metabolism

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.