title: 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.
authors.affiliation: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Tsunoda
authors.affiliation: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lamon-Fava
authors.affiliation: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Bela F
authors.initials: BF
authors.lastname: Asztalos
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, USA; Center for Neuroscience Research, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Lakshmanan K
authors.initials: LK
authors.lastname: Iyer
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Kris
authors.initials: K
authors.lastname: Richardson
authors.affiliation: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: Ernst.schaefer@tufts.edu.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001900:Boston; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000097:blood; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D000069463:Olive Oil / Q000008:administration & dosage; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D000069463:Olive Oil; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human
keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Gene expression; Hypoxia inducible factor 1; Microarray analysis; Peripheral blood mononuclear cells; α subunit