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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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