A gender-specific role for phosphatidylethanolamine N-methyltransferase-derived phosphatidylcholine in the regulation of plasma high density and very low density lipoproteins in mice.
Phosphatidylethanolamine N-methyltransferase (PEMT)is involved in a secondary pathway for production of phosphatidylcholine (PC) in liver. We fed Pemt-/-mice a high fat/high cholesterol diet for 3 weeks to determine whether or not PC derived from PEMT is required for very low density lipoprotein secretion. Lipid analyses of plasma and liver indicated that male Pemt-/- mice accumulated triacylglycerols in their livers and were unable to secrete the same amount of triacylglycerols from the liver as did Pemt+/+ mice. Plasma levels of triacylglycerol and both apolipoproteins B100 and B48 were significantly decreased only in male Pemt-/- mice. Experiments in which mice were injected with Triton WR1339 showed that, whereas hepatic apoB100 secretion was decreased in male Pemt-/- mice, the decrease in plasma apoB48 in male Pemt-/- mice was not due to reduced secretion. Moreover, female and, to a lesser extent, male Pemt-/- mice showed a striking 40% decrease in plasma PC and cholesterol in high density lipoproteins. These results suggest that, even though the content of hepatic PC was normal in PEMT-deficient mice, plasma lipoprotein levels were profoundly altered in a gender-specific manner.
Noga
Anna A
AA
Department of Biochemistry, Research Group on Molecular and Cell Biology of Lipids, Canadian Institutes for Health, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Vance
Dennis E
DE
D000821:Animal Feed; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002855:Chromatography, Thin Layer; D003902:Detergents / Q000494:pharmacology; D005260:Female; D005838:Genotype; D015151:Immunoblotting; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008079:Lipoproteins, VLDL / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000737:chemistry*; D050918:Phosphatidylethanolamine N-Methyltransferase; D010743:Phospholipids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D012737:Sex Factors; D013997:Time Factors; D000637:Transaminases / Q000097:blood; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D003902:Detergents; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D010713:Phosphatidylcholines; D010743:Phospholipids; D014280:Triglycerides; D011092:Polyethylene Glycols; D002784:Cholesterol; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D000637:Transaminases; C016811:tyloxapol