Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression

Abstract

Objective: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammation and cardiovascular disease (CVD). Our aim was to assess the effect of a six-week supplementation with either olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells (PBMC).

Methods: Subjects were sampled at baseline and six weeks after receiving either: olive oil 6.0 g/day (n = 16), EPA 1.8 g/day (n = 16), or DHA 1.8 g/day (n = 18). PBMC were subjected to gene expression analysis by microarray with key findings confirmed by quantitative real-time polymerase chain reaction (Q-PCR).

Results: Plasma phospholipid EPA increased 3 fold in the EPA group, and DHA increased 63% in the DHA group (both p < 0.01), while no effects were observed in the olive oil group. Microarray analysis indicated that EPA but not DHA or olive oil significantly affected the gene expression in the following pathways: 1) interferon signaling, 2) receptor recognition of bacteria and viruses, 3) G protein signaling, glycolysis and glycolytic shunting, 4) S-adenosyl-l-methionine biosynthesis, and 5) cAMP-mediated signaling including cAMP responsive element protein 1 (CREB1), as well as many other individual genes including hypoxia inducible factor 1, α subunit (HIF1A). The findings for CREB1 and HIF1A were confirmed by Q-PCR analysis.

Conclusions: Our data indicate that EPA supplementation was associated with significant effects on gene expression involving the interferon pathway as well as down-regulation of CREB1 and HIF1A, which may relate to its beneficial effect on CVD risk reduction.

Trial registration: ClinicalTrials.gov NCT01400490.

Keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Gene expression; Hypoxia inducible factor 1; Microarray analysis; Peripheral blood mononuclear cells; α subunit.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1

Mean (± SEM) relative changes in the expression of specific genes determined by quantitative real-time polymerase chain reaction (Q-PCR) in the three groups. Differences within each group were determined by paired t test (**p CCR6, chemokine (C-C motif) receptor 6; CREB1, cAMP responsive element binding protein 1; HIF1A, hypoxia-inducible factor 1-alpha; HMGB1, high mobility group box 1; IL1RN, interleukin 1 receptor antagonist; IL2RB, interleukin 2 receptor, beta; IRF7, interferon regulatory factor 7; STAT3, signal transducer and activator of transcription.