APOE genotype modifies the plasma oxylipin response to omega-3 polyunsaturated fatty acid supplementation in healthy individuals

Saleh, Rasha, West, Annette, Ostermann, Annika, Schebb, Nils Helge, Calder, Philip and Minihane, Anne-Marie (2021) APOE genotype modifies the plasma oxylipin response to omega-3 polyunsaturated fatty acid supplementation in healthy individuals. Frontiers in Nutrition, 8. ISSN 2296-861X

[img] PDF (Published_Version) - Published Version
Available under License Creative Commons Attribution.

Download (5MB)

Abstract

The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mediate inflammation in large part by affecting pro-inflammatory and anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the large inter-individual variation in oxylipin levels in response to n-3 PUFA supplementation, which in turn is likely to contribute to the overall heterogeneity in response to n-3 PUFA intervention. Given its known role in inflammation and as a modulator of the physiological response to EPA and DHA, here we explore, for the first time, the differential response of plasma hydroxy-, epoxy- and dihydroxy-arachidonic acid, EPA and DHA oxylipins according to apolipoprotein E (APOE) genotype using samples from a dose-response parallel design RCT. Healthy participants were given doses of EPA+DHA equivalent to intakes of 1, 2 and 4 portions of oily fish per week for twelve months. There was no difference in the plasma levels of EPA, DHA or ARA between the wildtype APOE3/E3 and APOE4 carrier groups after 3 months or 12 months of n-3 PUFA supplementation. At 12 months, hydroxy EPAs (HEPEs) and hydroxy-DHAs (HDHAs) were higher in APOE4 carriers, with the difference most evident at the highest EPA+DHA intake. A significant APOE*n-3 PUFA dose effect was observed for the CYP- hydroxylase products 19-HEPE (p=0.027) and 20-HEPE (p=0.011). 8-HEPE, which, along with several other plasma oxylipins, is an activator of peroxisome proliferator activated receptors (PPARs), showed the highest fold change in APOE4 carriers (14-fold) compared to APOE3/E3 (4-fold) (p=0.014). Low basal plasma EPA levels (EPA< 0.85% of total fatty acids) were associated with a geater change in 5-HEPE, 9-HEPE, 11-HEPE and 20-HEPE compared to high basal EPA levels(EPA> 1.22% of total fatty acids).In conclusion, APOE genotype modulated the plasma oxylipin response to increased EPA+DHA intake, with APOE4 carriers presenting with the greatest increases following high dose n-3 PUFA supplementation for twelve months.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 09 Sep 2021 00:22
Last Modified: 21 Sep 2021 01:33
URI: https://ueaeprints.uea.ac.uk/id/eprint/81346
DOI: 10.3389/fnut.2021.723813

Actions (login required)

View Item View Item