Providing lysophosphatidylcholine-bound omega-3 fatty acids increased eicosapentaenoic acid, but not docosahexaenoic acid, in the cortex of mice with the apolipoprotein E3 or E4 allele

Background: Several mechanisms have been proposed for the brain uptake of omega-3 fatty acids (n-3), including passive diffusion of the unesterified form and the use of Mfsd2a transporter for the lysophosphatidylcholine (LPC) form. We hypothesize that the accumulation of LPC n-3 in the brain is lower in mice carrying the apolipoprotein E epsilon 4 allele (APOE4), a major genetic risk factor for developing sporadic Alzheimer's disease in humans. Objective: Determine whether two or four months of supplementation with LPC n-3 increases the levels of docosahexaenoic acids (DHA) and eicosapentaenoic acids (EPA) in the frontal cortex of APOE3 and APOE4 mice. Methods: APOE3 and APOE4 mice were administered LPC n-3 (9.6 mg DHA + 18.3 mg EPA) or sunflower oil (control) by oral gavage for two or four months (n = 5-8 per genotype, per treatment, and per treatment duration). At the end of the treatment period, frontal cortices were collected, and their FA profiles analyzed by gas chromatography with flame ionization detection. Results: After two months of gavage with LPC n-3, APOE3 mice showed increased levels of EPA in their cortex, but not DHA. In APOE4 mice, neither EPA nor DHA levels were significantly affected. After four months of LPC n3, both APOE3 and APOE4 mice exhibited higher EPA levels, while changes in DHA levels were not statistically significant. Conclusion: LPC n-3 supplementation increased EPA, but not DHA, levels in the frontal cortex of mice in a duration- and APOE genotype-dependent manner. Further research is needed to explore the implications for brain health.