The influence of APOE genotype, DHA, and flavanol intervention on brain DHA and lipidomics profile in aged transgenic mice

Martinsen, Anneloes, Saleh, Rasha N. M., Chouinard-Watkins, Raphael, Bazinet, Richard, Harden, Glenn, Dick, James, Tejera, Noemi, Pontifex, Matthew G., Vauzour, David ORCID: and Minihane, Anne-Marie ORCID: (2023) The influence of APOE genotype, DHA, and flavanol intervention on brain DHA and lipidomics profile in aged transgenic mice. Nutrients, 15 (9). ISSN 2072-6643

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The apolipoprotein E4 (APOE4) 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 APOE4 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 APOE genotype is currently unknown. Here, using a humanised APOE3 and APOE4 targeted replacement transgenic mouse model, the interactive influence of cocoa flavanols (FLAV) and APOE 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 (p < 0.001) and brain (p = 0.001) following supplementation. Compared to APOE3, a higher red blood cell (RBC) DHA (p < 0.001) was evident in APOE4 mice following FO and FLAV supplementation. Although FO did not increase the percentage of brain DHA in APOE4, a 17.1% (p < 0.05) and 20.0% (p < 0.001) higher DHA level in the phosphatidylcholine (PC) fraction in the HF FO and HF FO FLAV groups, and a 14.5% (p < 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 APOE3 only (p < 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 APOE3.

Item Type: Article
Additional Information: Funding Information: The research was funded as part of a Biotechnology and Biological Sciences Research Council (BBSRC, BB/J004545/1) Institute Programme Grant.
Uncontrolled Keywords: alzheimer’s disease,apolipoprotein e,docosahexaenoic acid,brain,flavonoids,phospholipids,pufas,phospholipids,food science,nutrition and dietetics ,/dk/atira/pure/subjectarea/asjc/1100/1106
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 27 Apr 2023 10:30
Last Modified: 30 May 2023 14:30
DOI: 10.3390/nu15092032

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