The effects of N-6 polyunsaturated fatty acid supplementation on the lipidcomposition and atherogenesis in mouse models of atherosclerosis

Despite numerous studies, the precise role of dietary n-6 polyunsaturated f atty acids in the pathogenesis of atherosclerosis remains controversial. It has been shown that feeding an n-6-enriched diet resulted in decreased ath erosclerosis in African green monkeys and was associated with a reduction i n LDL levels. However, other authors reported that n-6 supplementation incr eased the oxidative stress and the susceptibility of LDL to undergo in vitr o oxidation, thus potentially enhancing atherosclerosis. The present study was designed to investigate the effect of dietary supplementation of n-6 po lyunsaturated fats (safflower oil), as compared with a saturated fat-rich d iet (Paigen), on the blood lipid profile and atherosclerosis in two mouse m odels. In the first experiment, female C57BL/6 mice (n = 23-30 per group) w ere fed a cholate containing Paigen diet, a safflower oil-rich diet (with c holate), or normal chow for 15 weeks. No significant differences between th e high fat diet groups were evident with respect to total cholesterol, LDL, HDL or triglyceride levels. The extent of aortic sinus fatty streaks did n ot differ significantly between the two groups. In the second experiment, L DL-receptor-deficient (LDL-RD) mice (n = 20-30 per group) were randomized i nto similar dietary regimens,Mice consuming a safflower oil-enriched diet d eveloped significantly less atherosclerosis, in comparison with Paigen diet -fed mice. A reduction in LDL levels, although not of a similar magnitude a s the reduction in atherosclerosis, was evident in the safflower oil-fed mi ce when compared to the Paigen diet-fed littermates. In both mouse models o f atherosclerosis, LDL isolated from the plasma of mice on the n-6 polyunsa turated diet was rendered slightly more susceptible to oxidation in vitro, as indicated by a shorter lag period for diene formation. Thus, the effects of n-6 fatty acids on the lipoprotein composition and other potential infl uences may have contributed to the anti-atherogenic effect in the LDL-RD mo use model. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.