Insights into the requirement of phosphatidylcholine synthesis for liver function in mice.
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.
Noga
Anna A
AA
Department of Biochemistry and CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada.
Vance
Dennis E
DE
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D002784:Cholesterol / Q000008:administration & dosage / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism; D005223:Fats / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D005838:Genotype; D007553:Isotope Labeling; D008099:Liver / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D010713:Phosphatidylcholines / Q000096:biosynthesis* / Q000097:blood; D050918:Phosphatidylethanolamine N-Methyltransferase; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011092:Polyethylene Glycols
D001055:Apolipoproteins B; D005223:Fats; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D011092:Polyethylene Glycols; D002784:Cholesterol; D008715:Methionine; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D019916:Choline-Phosphate Cytidylyltransferase; C016811:tyloxapol