Reduction in dietary omega-6 polyunsaturated fatty acids: Eicosapentaenoic acid plus docosahexaenoic acid ratio minimizes atherosclerotic lesion formation and inflammatory response in the LDL receptor null mouse

Abstract

Dietary very long chain omega (ω)-3 polyunsaturated fatty acids (PUFA) have been associated with reduced CVD risk, the mechanisms of which have yet to be fully elucidated. LDL receptor null mice (LDLr−/−) were used to assess the effect of different ratios of dietary ω-6 PUFA to eicosapentaenoic acid plus docosahexaenoic acid (ω-6:EPA + DHA) on atherogenesis and inflammatory response. Mice were fed high saturated fat diets without EPA and DHA (HSF ω-6), or with ω-6:EPA + DHA at ratios of 20:1 (HSF R = 20:1), 4:1 (HSF R = 4:1), and 1:1 (HSF R = 1:1) for 32 weeks. Mice fed the lowest ω-6:EPA + DHA ratio diet had lower circulating concentrations of non-HDL cholesterol (25%, P < 0.05) and interleukin-6 (IL-6) (44%, P < 0.05) compared to mice fed the HSF ω-6 diet. Aortic and elicited peritoneal macrophage (Mϕ) total cholesterol were 24% ( P = 0.07) and 25% ( P < 0.05) lower, respectively, in HSF R = 1:1 compared to HSF ω-6 fed mice. MCP-1 mRNA levels and secretion were 37% ( P < 0.05) and 38% ( P < 0.05) lower, respectively, in elicited peritoneal Mϕ isolated from HSF R = 1:1 compared to HSF ω-6 fed mice. mRNA and protein levels of ATP-binding cassette A1, and mRNA levels of TNFα were significantly lower in elicited peritoneal Mϕ isolated from HSF R = 1:1 fed mice, whereas there was no significant effect of diets with different ω-6:EPA + DHA ratios on CD36, Mϕ scavenger receptor 1, scavenger receptor B1 and IL-6 mRNA or protein levels. These data suggest that lower ω-6:EPA + DHA ratio diets lowered some measures of inflammation and Mϕ cholesterol accumulation, which was associated with less aortic lesion formation in LDLr−/− mice.