Protective role of n6/n3 PUFA supplementation with varying DHA/EPA ratios against atherosclerosis in mice

J Nutr Biochem. 2016 Jun:32:171-80. doi: 10.1016/j.jnutbio.2016.02.010. Epub 2016 Mar 21.

Abstract

The effects of n3 polyunsaturated fatty acids (PUFA) on cardiovascular disease are controversial. We currently explored the effects of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on high-fat-induced atherosclerosis. In model apoE(-/-) mice, high-fat diets (HFD) were partially replaced with fish and algal oils (DHA/EPA 2:1, 1:1 and 1:2) and/or plant oils enriched in linoleic and alpha-linolenic acids with an n6/n3 ratio of 4:1. PUFA supplementation significantly reduced the atherosclerotic plaque area, serum lipid profile, inflammatory response, aortic ROS production, proinflammatory factors and scavenger receptor expression as compared to those in the HFD group. However, plant oils did not have a significant effect on the following: serum HDL-C level; aortic ABCA1, ABCG1 and LAL mRNA expression; and CD36 and LOX-1 protein expression. Compared to the plant-oil-treated group, the DHA/EPA 1:1 group had a smaller atherosclerotic plaque area, higher serum HDL-C levels and lesser CD36 and MSR-1 mRNA expression; the DHA/EPA 2:1 group had lower serum TC, LDL-C and TNF-α levels and lower aortic ROS levels. Our study suggested that n3 PUFA from animals had more potent atheroprotective effects than that from plants. Supplementation involving higher DHA/EPA ratios and an n6/n3 ratio of 4:1 was beneficial for reducing serum "bad cholesterol" and a 1:1 DHA/EPA ratio with an n6/n3 ratio of 4:1 was beneficial for improving serum "good cholesterol" and inhibiting ox-LDL uptake. Our results suggest that achieving an n6/n3 ratio of 4:1 in the diet is also important in addition to having an optimal DHA/EPA ratio.

Keywords: Alpha-linolenic acid; Atherosclerosis; DHA/EPA; Docosahexaenoic acid; Eicosapentaenoic acid; n3 PUFA.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / metabolism
  • Animals
  • Aorta / immunology
  • Aorta / metabolism
  • Aorta / pathology*
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Diet, High-Fat / adverse effects
  • Dietary Supplements* / analysis
  • Fatty Acids, Omega-3 / analysis
  • Fatty Acids, Omega-3 / therapeutic use*
  • Fatty Acids, Omega-6 / analysis
  • Fatty Acids, Omega-6 / therapeutic use*
  • Fish Oils / chemistry
  • Fish Oils / therapeutic use
  • Gene Expression Regulation
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plant Oils / chemistry
  • Plant Oils / therapeutic use
  • Random Allocation
  • Receptors, Scavenger / genetics
  • Receptors, Scavenger / metabolism
  • Sterol Esterase / genetics
  • Sterol Esterase / metabolism
  • Sunflower Oil
  • alpha-Linolenic Acid / chemistry
  • alpha-Linolenic Acid / therapeutic use

Substances

  • ABCA1 protein, mouse
  • ABCG1 protein, mouse
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • Apolipoproteins E
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fish Oils
  • Plant Oils
  • Receptors, Scavenger
  • Sunflower Oil
  • alpha-Linolenic Acid
  • perilla seed oil
  • Sterol Esterase
  • lysosomal acid lipase, mouse