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

Author
item TSUNODA, FUMIYOSHI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ASZTALOS, BELA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item IYER, LAKSHMANAN - Tufts - New England Medical Center
item RICHARDSON, KRIS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SCHAEFER, ERNST - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/12/2015
Publication Date: 8/1/2015
Citation: Tsunoda, F., Lamon-Fava, S., Asztalos, B.F., Iyer, L.K., Richardson, K., Schaefer, E.J. 2015. Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression. Atherosclerosis. 241(2):400-408.

Interpretive Summary: Fish and fish oil contain two types of fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Population studies and clinical intervention studies suggest that consumption of fish and fish oil reduces the risk or severity of several chronic inflammatory diseases, like cardiovascular disease. The goal of our study was to assess the common and different effects of these fatty acids on inflammation. Healthy subjects received 1.8 g/day of either EPA or DHA or a control oil (olive oil) for 6 weeks. We obtained a subset of white blood cells, mononuclear cells, at baseline and at the end of treatment and measured the expression of several genes. We found that EPA, but not DHA, affected cellular immune responses including the interferon signaling pathway and lowered the expression of inflammatory genes. We conclude that EPA has a stronger anti-inflammatory effect than DHA.

Technical 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, alpha 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.