A Gender-Specific Role for Phosphatidylethanolamine N-methyltransferase-derived Phosphatidylcholine in the Regulation of Plasma High Density and Very Low Density Lipoproteins in Mice

J Biol Chem. 2003 Jun 13;278(24):21851-9. doi: 10.1074/jbc.M301982200. Epub 2003 Mar 31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed
  • Animals
  • Apolipoproteins B / metabolism
  • Cholesterol / metabolism
  • Chromatography, Thin Layer
  • Detergents / pharmacology
  • Female
  • Genotype
  • Immunoblotting
  • Lipid Metabolism
  • Lipoproteins, HDL / chemistry*
  • Lipoproteins, VLDL / chemistry*
  • Liver / metabolism
  • Male
  • Methyltransferases / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylcholines / chemistry*
  • Phosphatidylethanolamine N-Methyltransferase
  • Phospholipids / metabolism
  • Polyethylene Glycols / pharmacology
  • Sex Factors
  • Time Factors
  • Transaminases / blood
  • Triglycerides / metabolism

Substances

  • Apolipoproteins B
  • Detergents
  • Lipoproteins, HDL
  • Lipoproteins, VLDL
  • Phosphatidylcholines
  • Phospholipids
  • Triglycerides
  • Polyethylene Glycols
  • Cholesterol
  • Methyltransferases
  • Phosphatidylethanolamine N-Methyltransferase
  • Transaminases
  • tyloxapol