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Journal of Lipid Research, Vol. 44, 1998-2005, October 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology
Insights into the requirement of phosphatidylcholine synthesis for liver function in mice
Department of Biochemistry and CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada
1 To whom correspondence should be addressed. e-mail: dennis.vance{at}ualberta.ca
Phosphatidylcholine (PC) is made in the liver by the CDP-choline pathway and via phosphatidylethanolamine N-methyltransferase (PEMT), which catalyzes the conversion of phosphatidylethanolamine to PC. Unexpectedly, hepatic apolipoprotein B-100 secretion is inhibited in male, but not female, Pemt-/- mice (Noga, A. A., Y. Zhao, and D. E. Vance. 2002. J. Biol. Chem. 277: 42358–42365; Noga, A. A., and D. E. Vance. 2003. J. Biol. Chem. 278: 21851–21859). To gain further insight into this process, we compared PC metabolism in male and female mice fed chow or a high-fat/high-cholesterol (HF/HC) diet. Immunoblot analyses demonstrated that twice as much PEMT2 was present in livers from female compared with male mice. In contrast, assays of CTP:phosphocholine cytidylyltransferase from livers of Pemt+/+ mice demonstrated more active cytidylyltransferase in male than in female mice. Secretion of PEMT-derived PC into lipoproteins was examined in vivo by injection of mice with [methyl-3H]methionine in the presence of Triton WR1339. The PEMT-derived PC shifts to smaller-sized particles in response to a HF/HC diet, but only in male mice. Secretion of PEMT-derived PC into bile was enhanced in mice fed a HF/HC diet.
These results demonstrate that the synthesis and targeting of PC produced by the PEMT pathway in the livers of mice differs in a gender- and diet-specific manner.
Abbreviations: CT, CTP:phosphocholine cytidylyltransferase; ER, endoplasmic reticulum; HF/HC, high-fat/high-cholesterol; MAM, mitochondria-associated membranes; PC, phosphatidylcholine; PEMT, phosphatidylethanolamine N-methyltransferase
Supplementary key words phosphatidylethanolamine N-methyltransferase • CTP:phosphocholine cytidylyltransferase • gender • diet
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