High Dietary n-6/n-3 PUFA Ratio Promotes HDL Cholesterol Level, but Does Not Suppress Atherogenesis in Apolipoprotein E-null Mice 1

J Atheroscler Thromb. 2009 Aug;16(4):463-71. doi: 10.5551/jat.no1347. Epub 2009 Sep 3.


Aim: Dietary fatty acids affect atherogenesis, which was presumed to be partly related to HDL cholesterol (HDL-C) metabolism. The major aim of the work was to analyze various ratios of n-6/n-3 PUFA diets on HDL-C metabolism in apolipoprotein E-null (apoE(-/-)) mice, which have similar symptoms to human type III familial hyperlipoproteinemia.

Methods: Two-month-old male apoE(-/-) mice were fed four types of n-6/n-3 PUFA diet (group 1, 1.28; group 2, 5.03; group 3, 9.98 and group 4, 68.26) and control diet, respectively, for 6 weeks. With respect to serum apolipoprotein (apo) A-I concentration, lecithin-cholesterol acyltransferase (LCAT) activity and mRNA abundance of genes involved in HDL-C metabolism in the liver were analyzed.

Results: Group 4 diet significantly increased the plasma HDL-C and apoA-I concentrations compared with other groups. LCAT activity in serum increased with decreased ratios of n-6/n-3 PUFA. As the dietary ratio of n-6/n-3 fatty acids increased, so did mRNA levels of hepatic apoA-I, scavenger receptor B class-1 (SR-B1), LCAT, ATP binding cassette transporter A1 (ABCA1), ABCG1 and liver X receptor alpha (LXRalpha). ApoA-II mRNA level, however, had a tendency to fall. Group 4 diet increased apoA-I and ABCA1 and decreased apoA-II transcriptional levels, whereas group 1 diet decreased mRNA levels of apoA-I, LCAT, SR-B1 and ABCG1.

Conclusion: Our data indicated that a high ratio of n-6/n-3 PUFA increased the serum HDL-C level, but did not effectively suppress atherogenesis in apoE(-/-) mice. The elevated HDL-C level is possibly due to up-regulated hepatic apoA-I and ABCA1 with suppression of apoA-Ii expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency*
  • Atherosclerosis / prevention & control*
  • Cholesterol, HDL / blood*
  • Cholesterol, HDL / metabolism
  • Dietary Fats / pharmacology
  • Fatty Acids, Omega-3 / pharmacology*
  • Fatty Acids, Omega-6 / pharmacology*
  • Lipid Metabolism
  • Mice
  • Mice, Knockout
  • Transcription, Genetic / drug effects


  • Apolipoproteins E
  • Cholesterol, HDL
  • Dietary Fats
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6