The fatty acid composition of chylomicron remnants influences their propensity to oxidate

BACKGROUND AND AIM: Although the replacement of saturated with unsaturated dietary fat has been advocated as a means of reducing the risk of cardiovascular disease, diets high in polyunsaturated fatty acids (PUFAs) may increase lipid peroxidation, thus contributing to the pathogenesis of atherosclerosis. As the susceptibility of individual fatty acids to oxidation directly depends on their degree of unsaturation, and the oxidative modification of lipoproteins may be an important determinant of atherogenesis, the aim of this study was to evaluate the susceptibility to auto-oxidation and copper-mediated oxidation of chylomicron remnants (CMRs) enriched in n-3 or n-6 PUFA. METHODS AND RESULTS: The remnants were prepared in vitro from chylomicrons obtained from rats given an oral dose of fish or corn oil, using rat plasma containing lipoprotein lipase. Their propensity to oxidate and the extent of the oxidation were estimated by measuring the formation of conjugated dienes and the detrimental products of lipid peroxidation. The results showed that: 1) the corn oil CMRs contained a relatively high proportion of n-6 PUFA (mainly linoleic acid), whereas the fish oil CMRs contained more n-3 PUFA, mainly eicosapentanoic and docosahexaenoic acids; 2) n-3-rich CMRs have a significantly lower propensity to oxidate than n-6-rich CMRs despite their 50% lower alpha-tocopherol content and 40% higher unsaturation index. CONCLUSION: Our data indicate that the precise allocation of n-3 PUFA within the lipid core of CMRs may play a pivotal role in lowering the susceptibility to oxidation of fish CMRs by overcoming the effects of unfavourable alpha-tocopherol concentration. Eating n-3 rather than n-6 PUFAs seems to make CMRs more resistant against free radical attack, which may contribute to attenuating their potential atherogenic properties.