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J. Biol. Chem., Vol. 278, Issue 24, 21851-21859, June 13, 2003
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From the Department of Biochemistry and Canadian Institutes for Health Research Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
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.
Received for publication, February 25, 2003
* This work was supported in part by grants from the Heart and Stroke Foundations of Alberta, the Northwest Territories, and Nunavut. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Supported by a Studentship Award from the Heart and Stroke Foundation of Canada.
Medical Scientist of the Alberta Heritage Foundation for Medical Research and holder of the Canada Research Chair for the Molecular and Cell Biology of Lipids. To whom correspondence should be addressed. Tel.: 780-492-8286; Fax: 780-492-3383; E-mail: dennis.vance{at}ualberta.ca.
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