Abstract
BackgroundDietary fish oil, rich in n-3 fatty acids (n-3 FAs), e.g. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), regulate inflammatory reactions by various mechanisms, e.g. gene activation. However, the effects of long-term treatment with DHA and EPA in humans, using genome wide techniques, are poorly described. Hence, our aim was to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global gene expression in peripheral blood mononuclear cells.Methods and FindingsIn the present study, blood samples were obtained from a subgroup of 16 patients originating from the randomized double-blind, placebo-controlled OmegAD study, where 174 Alzheimer disease (AD) patients received daily either 1.7 g of DHA and 0.6 g EPA or placebo for 6 months. In blood samples obtained from 11 patients receiving n-3 FA and five placebo, expressions of approximately 8000 genes were assessed by gene array. Significant changes were confirmed by real-time PCR. At 6 months, the n-3 FAs group displayed significant rises of DHA and EPA plasma concentrations, as well as up- and down-regulation of nine and ten genes, respectively, was noticed. Many of these genes are involved in inflammation regulation and neurodegeneration, e.g. CD63, MAN2A1, CASP4, LOC399491, NAIP, and SORL1 and in ubiqutination processes, e.g. ANAPC5 and UBE2V1. Down-regulations of ANAPC5 and RHOB correlated to increases of plasma DHA and EPA levels.ConclusionsWe suggest that 6 months of dietary n-3 FA supplementation affected expression of genes that might influence inflammatory processes and could be of significance for AD.Trial RegistrationClinicalTrials.gov NCT00211159
Highlights
Omega-3 fatty acids (n-3 FAs), e.g. eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3), present in marine oils, modulate inflammatory reactions and ameliorate symptoms of several autoimmune and other inflammatory disorders [1], [2]
We suggest that 6 months of dietary n-3 fatty acids (n-3 FAs) supplementation affected expression of genes that might influence inflammatory processes and could be of significance for Alzheimer’s disease (AD)
In the n-3 FAs group plasma values for DHA as well as for EPA were significantly higher at 6 months compared with pre-trial values (p = 0.00006 and p = 0.00004 respectively)
Summary
Omega-3 fatty acids (n-3 FAs), e.g. eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3), present in marine oils, modulate inflammatory reactions and ameliorate symptoms of several autoimmune and other inflammatory disorders [1], [2]. Previous investigations on effects of DHA and/or EPA on gene expressions in animal studies and in vitro models have shown changes in a variety of genes, some of which are believed to be involved in inflammation and chronic neurodegenerative disorder. These gene expression studies have mostly been conducted after a short time exposure and on small sets of genes [11], [12], [13], [14], [15], [16], [17], [18]. Rich in n-3 fatty acids (n-3 FAs), e.g. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), regulate inflammatory reactions by various mechanisms, e.g. gene activation. Our aim was to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global gene expression in peripheral blood mononuclear cells
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