title: Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men.
abstract: Our previous study with docosahexaenoic acid (DHA) supplementation to hypertriglyceridemic men showed that DHA reduced several risk factors for cardiovascular disease, including the plasma concentration of inflammatory markers. To determine the effect of DHA supplementation on the global gene expression pattern, we performed Affymetrix GeneChip microarray analysis of blood cells [treated with lipopolysaccharide (LPS) or vehicle] drawn before and after the supplementation of DHA from the hypertriglyceridemic men who participated in that study. Genes that were significantly differentially regulated by the LPS treatment and DHA supplementation were identified. Differential regulation of 18 genes was then verified by quantitative real-time polymerase chain reaction (qRT-PCR). Both microarray and qRT-PCR data showed that DHA supplementation significantly suppressed the expression of low-density lipoprotein (LDL) receptor and cathepsin L1, both of which were also up-regulated by LPS. DHA supplementation also suppressed oxidized LDL (lectin-like) receptor 1 (OLR1). However, LPS did not induce OLR1 mRNA expression. Enrichment with Gene Ontology categories demonstrated that the genes related to transcription factor activity, immunity, host defense and inflammatory responses were inversely regulated by LPS and DHA. These results provide supporting evidence for the anti-inflammatory effects of DHA supplementation, and reveal previously unrecognized genes that are regulated by DHA and are associated with risk factors of cardiovascular diseases.
authors.affiliation: Center of Excellence in Nutritional Genomics, University of California Davis, Davis, CA 95616, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Dawson
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Adkins
authors.forename: Madhuri
authors.initials: M
authors.lastname: Vemuri
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Rodriguez
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Gregg
authors.forename: Darshan S
authors.initials: DS
authors.lastname: Kelley
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Hwang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D056668:Cathepsin L / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016032:Randomized Controlled Trials as Topic; D060888:Real-Time Polymerase Chain Reaction; D011973:Receptors, LDL / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; C495137:OLR1 protein, human; D011973:Receptors, LDL; D051127:Scavenger Receptors, Class E; D004281:Docosahexaenoic Acids; C534281:CTSL protein, human; D056668:Cathepsin L