Phosphatidylethanolamine-N-methyltransferase activity and dietary choline regulate liver-plasma lipid flux and essential fatty acid metabolism in mice.
Phosphatidylethanolamine-N-methyltransferase (PEMT) catalyzes the methylation of phosphatidylethanolamine to form phosphatidylcholine (PC) and represents one of the two major pathways for PC biosynthesis. Mice with a homozygous disruption of the PEMT gene are dependent on the 1,2-diacylglycerol cholinephosphotransferase (CDP-choline) pathway for the synthesis of PC and develop severe liver steatosis when fed a diet deficient in choline. The present study used quantitative lipid metabolite profiling to characterize lipid metabolism in PEMT-deficient mice fed diets containing varying concentrations of choline. Choline supplementation restored liver, but not plasma PC concentrations of PEMT-deficient mice to levels commensurate with control mice. Choline supplementation also restored plasma triglyceride concentrations to normal levels, but did not restore plasma cholesterol ester concentrations in the PEMT-deficient mice to those equal to control mice. PEMT-deficient mice also had substantially diminished concentrations of docosahexaenoic acid [22:6(n-3)] and arachidonic acid [20:4(n-6)] in plasma, independent of choline status. Thus, choline supplementation rescued some but not all of the phenotypes induced by the knockout. These findings indicate that PEMT activity functions beyond its recognized role as a compensatory pathway for PC biosynthesis and that, in contrast, PEMT activity is involved in many physiologic processes including the flux of lipid between liver and plasma and the delivery of essential fatty acids to blood and peripheral tissues via the liver-derived lipoproteins.
Watkins
Steven M
SM
Lipomics Technologies, Incorporated, West Sacramento, CA 95691, USA. steve.watkins@lipomics.com
Zhu
Xiaonan
X
Zeisel
Steven H
SH
D000818:Animals; D002788:Cholesterol Esters / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D005228:Fatty Acids, Essential / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008780:Methyltransferases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D050918:Phosphatidylethanolamine N-Methyltransferase; D010743:Phospholipids / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D002788:Cholesterol Esters; D005228:Fatty Acids, Essential; D008055:Lipids; D010743:Phospholipids; D014280:Triglycerides; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D002794:Choline