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Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood mononuclear leukocytes: the OmegAD study.

Abstract

BACKGROUND

Dietary 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 FINDINGS

In 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.

CONCLUSIONS

We 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 REGISTRATION

ClinicalTrials.gov NCT00211159.

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  • Authors+Show Affiliations

    ,

    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden. inger.vedin@ki.se

    , , , , , , , ,

    Source

    PloS one 7:4 2012 pg e35425

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Dietary Supplements
    Docosahexaenoic Acids
    Eicosapentaenoic Acid
    Fatty Acids, Omega-3
    Female
    Gene Expression Regulation
    Humans
    Leukocytes, Mononuclear
    Male
    Transcriptome

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22545106

    Citation

    Vedin, Inger, et al. "Effects of DHA-rich N-3 Fatty Acid Supplementation On Gene Expression in Blood Mononuclear Leukocytes: the OmegAD Study." PloS One, vol. 7, no. 4, 2012, pp. e35425.
    Vedin I, Cederholm T, Freund-Levi Y, et al. Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood mononuclear leukocytes: the OmegAD study. PLoS ONE. 2012;7(4):e35425.
    Vedin, I., Cederholm, T., Freund-Levi, Y., Basun, H., Garlind, A., Irving, G. F., ... Palmblad, J. (2012). Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood mononuclear leukocytes: the OmegAD study. PloS One, 7(4), pp. e35425. doi:10.1371/journal.pone.0035425.
    Vedin I, et al. Effects of DHA-rich N-3 Fatty Acid Supplementation On Gene Expression in Blood Mononuclear Leukocytes: the OmegAD Study. PLoS ONE. 2012;7(4):e35425. PubMed PMID: 22545106.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood mononuclear leukocytes: the OmegAD study. AU - Vedin,Inger, AU - Cederholm,Tommy, AU - Freund-Levi,Yvonne, AU - Basun,Hans, AU - Garlind,Anita, AU - Irving,Gerd Faxén, AU - Eriksdotter-Jönhagen,Maria, AU - Wahlund,Lars-Olof, AU - Dahlman,Ingrid, AU - Palmblad,Jan, Y1 - 2012/04/24/ PY - 2011/06/29/received PY - 2012/03/16/accepted PY - 2012/5/1/entrez PY - 2012/5/1/pubmed PY - 2012/8/28/medline SP - e35425 EP - e35425 JF - PloS one JO - PLoS ONE VL - 7 IS - 4 N2 - BACKGROUND: Dietary 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 FINDINGS: In 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. CONCLUSIONS: We 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 REGISTRATION: ClinicalTrials.gov NCT00211159. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22545106/Effects_of_DHA_rich_n_3_fatty_acid_supplementation_on_gene_expression_in_blood_mononuclear_leukocytes:_the_OmegAD_study_ L2 - http://dx.plos.org/10.1371/journal.pone.0035425 DB - PRIME DP - Unbound Medicine ER -