The Influence of Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic Mice.

The apolipoprotein E4 () genotype is predictive of Alzheimer's disease (AD). The brain is highly enriched with the omega-3 polyunsaturated fatty acid (n3-PUFA), docosahexaenoic acid (DHA). DHA's metabolism is defective in carriers. Flavanol intake can play a role in modulating DHA levels. However, the impact of flavanol co-supplementation with fish oil on brain DHA uptake, status and partitioning, and according to genotype is currently unknown. Here, using a humanised and targeted replacement transgenic mouse model, the interactive influence of cocoa flavanols (FLAV) and genotype on the blood and subcortical brain PUFA status following the supplementation of a high fat (HF) enriched with DHA from fish oil (FO) was investigated. DHA levels increased in the blood ( < 0.001) and brain ( = 0.001) following supplementation. Compared to a higher red blood cell (RBC) DHA ( < 0.001) was evident in mice following FO and FLAV supplementation. Although FO did not increase the percentage of brain DHA in a 17.1% ( < 0.05) and 20.0% ( < 0.001) higher DHA level in the phosphatidylcholine (PC) fraction in the HF FO and HF FO FLAV groups, and a 14.5% ( < 0.05) higher DHA level in the phosphatidylethanolamine (PE) fraction in the HF FO FLAV group was evident in these animals relative to the HF controls. The addition of FLAV (+/- FO) did not significantly increase the percentage of brain DHA in the group as a whole. However, a higher brain: RBC DHA ratio was evident in only ( < 0.05) for HF FLAV versus HF. In conclusion, our data shows only modest effects of FLAV on the brain DHA status, which is limited to