Low n-6/n-3 PUFA Ratio Improves Lipid Metabolism, Inflammation, Oxidative Stress and Endothelial Function in Rats Using Plant Oils as n-3 Fatty Acid Source

Lipids. 2016 Jan;51(1):49-59. doi: 10.1007/s11745-015-4091-z. Epub 2015 Nov 2.


Lipid metabolism, inflammation, oxidative stress and endothelial function play important roles in the pathogenesis of cardiovascular disease (CVD), which may be affected by an imbalance in the n-6/n-3 polyunsaturated fatty acid (PUFA) ratio. This study aimed to investigate the effects of the n-6/n-3 PUFA ratio on these cardiovascular risk factors in rats fed a high-fat diet using plant oils as the main n-3 PUFA source. The 1:1 and 5:1 ratio groups had significantly decreased serum levels of total cholesterol, low-density lipoprotein cholesterol, and proinflammatory cytokines compared with the 20:1 group (p < 0.05). Additionally, the 20:1 group had significantly increased serum levels of E-Selectin, von Willebrand factor (vWF), and numerous markers of oxidative stress compared with the other groups (p < 0.05). The 1:1 group had a significantly decreased lipid peroxide level compared with the other groups (p < 0.05). Serum levels of malondialdehyde, reactive oxygen species and vWF tended to increase with n-6/n-3 PUFA ratios increasing from 5:1 to 20:1. We demonstrated that low n-6/n-3 PUFA ratio (1:1 and 5:1) had a beneficial effect on cardiovascular risk factors by enhancing favorable lipid profiles, having anti-inflammatory and anti-oxidative stress effects, and improving endothelial function. A high n-6/n-3 PUFA ratio (20:1) had adverse effects. Our results indicated that low n-6/n-3 PUFA ratios exerted beneficial cardiovascular effects, suggesting that plant oils could be used as a source of n-3 fatty acids to prevent CVD. They also suggested that we should be aware of possible adverse effects from excessive n-3 PUFA.

Keywords: Atherosclerosis; Edible oils; Inflammation; Lipid metabolism; Lipid peroxidation; Plant lipid biochemistry; n-3 Fatty acids; n-6 Fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / blood
  • Cytokines / metabolism
  • Diet
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-3 / pharmacology
  • Fatty Acids, Omega-6 / administration & dosage
  • Fatty Acids, Omega-6 / metabolism*
  • Fatty Acids, Omega-6 / pharmacology
  • Glucose / analysis
  • Inflammation / metabolism*
  • Insulin / analysis
  • Lipid Metabolism / drug effects*
  • Male
  • Oxidative Stress / drug effects*
  • Plant Oils / chemistry
  • Plant Oils / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides / metabolism


  • Cytokines
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Insulin
  • Plant Oils
  • Triglycerides
  • Glucose