Differential Effect of Dietary Supplementation with a Soybean Oil Enriched in Oleic Acid versus Linoleic Acid on Plasma Lipids and Atherosclerosis in LDLR-Deficient Mice

Int J Mol Sci. 2022 Jul 29;23(15):8385. doi: 10.3390/ijms23158385.


Both monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) play important roles in lipid metabolism, and diets enriched with either of these two fatty acids are associated with decreased cardiovascular risk. Conventional soybean oil (CSO), a common food ingredient, predominantly contains linoleic acid (LA; C18:2), a n-6 PUFA. Recently, a modified soybean oil (MSO) enriched in oleic acid (C18:1), a n-9 MUFA, has been developed, because of its improved chemical stability to oxidation. However, the effect of the different dietary soybean oils on cardiovascular disease remains unknown. To test whether diets rich in CSO versus MSO would attenuate atherosclerosis development, LDL receptor knock-out (LDLR-KO) mice were fed a Western diet enriched in saturated fatty acids (control), or a Western diet supplemented with 5% (w/w) LA-rich CSO or high-oleic MSO for 12 weeks. Both soybean oils contained a similar amount of linolenic acid (C18:3 n-3). The CSO diet decreased plasma lipid levels and the cholesterol content of VLDL and LDL by approximately 18% (p < 0.05), likely from increased hepatic levels of PUFA, which favorably regulated genes involved in cholesterol metabolism. The MSO diet, but not the CSO diet, suppressed atherosclerotic plaque size compared to the Western control diet (Control Western diet: 6.5 ± 0.9%; CSO diet: 6.4 ± 0.7%; MSO diet: 4.0 ± 0.5%) (p < 0.05), independent of plasma lipid level changes. The MSO diet also decreased the ratio of n-6/n-3 PUFA in the liver (Control Western diet: 4.5 ± 0.2; CSO diet: 6.1 ± 0.2; MSO diet: 2.9 ± 0.2) (p < 0.05), which correlated with favorable hepatic gene expression changes in lipid metabolism and markers of systemic inflammation. In conclusion, supplementation of the Western diet with MSO, but not CSO, reduced atherosclerosis development in LDLR-KO mice independent of changes in plasma lipids.

Keywords: atherosclerosis; inflammation; modified soybean oil; monounsaturated fatty acids (MUFA); n-6/n-3 PUFA ratio; polyunsaturated fatty acids (PUFA).

MeSH terms

  • Animals
  • Atherosclerosis*
  • Cholesterol / metabolism
  • Dietary Supplements
  • Fatty Acids / metabolism
  • Fatty Acids, Monounsaturated / metabolism
  • Fatty Acids, Omega-3*
  • Fatty Acids, Unsaturated / metabolism
  • Linoleic Acid
  • Mice
  • Mice, Knockout
  • Oleic Acid
  • Receptors, LDL / genetics
  • Soybean Oil


  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • Receptors, LDL
  • Oleic Acid
  • Soybean Oil
  • Cholesterol
  • Linoleic Acid

Grants and funding

This research was supported by the Intramural Research Program of the National Heart, Lung and Blood Institute (NHLBI) (HL006095) at the National Institutes of Health.