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.