Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of blood cells from hypertriglyceridemic men treated with docosahexaenoic acid shows suppression of LDLR and OLR1 gene expression.

ABSTRACT: Previously published results from our double-blind, placebo-controlled parallel study with docosahexaenoic acid (DHA) supplementation (3 g/d, 90 d) to hypertriglyceridemic men (39-66yr) showed that DHA reduced several risk factors for cardiovascular disease (CVD), 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 from the hyperlipidemic men who participated in the previous study. Genes that were significantly differentially regulated by the LPS treatment and DHA supplementation were identified. Differential regulation of 18 genes was then confirmed by quantitative RT-PCR. Both microarray and qRT-PCR data showed that the expression of LDL receptor (LDLR), oxidized LDL receptor (OLR1), and cathepsin L1 (CTSL) was significantly suppressed by DHA supplementation; however, LPS stimulated the expression of LDLR and CTSL but not that of OLR1. LPS up-regulated and DHA suppressed the expression of prostaglandin E synthase (PTGES), PPAR delta, and various chemokines. Enrichment with Gene Ontology categories demonstrated that the genes related to transcription factor activity, immune responses, host defense responses, inflammatory responses, and apoptosis 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. Double-blind, placebo-controlled parallel study with DHA supplementation to hypertriglyceridemic men. Gene expression detected in LPS-stimulated (LPS) and unstimulated (vehicle) white blood cells. 3-4 replicates per group.

ORGANISM(S): Homo sapiens

SUBMITTER: Daniel Hwang

PROVIDER: E-GEOD-20114 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men.

Dawson Kevin K Zhao Ling L Adkins Yuriko Y Vemuri Madhuri M Rodriguez Raymond L RL Gregg Jeffrey P JP Kelley Darshan S DS Hwang Daniel H DH

The Journal of nutritional biochemistry 20110719 6

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 hypertri ...[more]

PMID: 21775114

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Project description:Fish oil supplementation is generally seen as beneficial for human health, due to the presence of n-3 polyunsaturated fatty acids (n-3 PUFAs). These fatty acids can elicit their effect through changes in gene expression. Effects of n-3 PUFAs on gene expression of inflammatory and atherogenic markers have been shown in several in vitro and animal studies. However, little evidence is available on human in vivo studies on n-3 PUFA related gene expression. In the present study we investigate the effects of EPA and DHA supplementation for 6 months on gene expression profiles of peripheral blood mononuclear cells (PBMCs). Whole genome microarray analysis was performed on PBMC RNA from subjects who received 1.8 grams of EPA and DHA in capsules (n=23) or capsules containing high oleic acid sunflower oil (HOSF)(n=25). Intake of EPA and DHA resulted in a change of 1040 genes. We found a down-regulation in inflammatory and atherogenic related pathways, such as NF-ÎºB signaling, eicosanoid synthesis, scavenger receptors activity and cell adhesion. These results seem to point to an improvement in health status, in which lymphocytes are less prone to produce chemokines and adhesion molecules and monocytes show reduced susceptibility to differentiate into foam cells. Overall, beneficial effects of n-3 PUFAs that have been described in vitro and in animal studies, were shown in vivo in human subjects in this study. This not only confirms that EPA and DHA elicits beneficial effects on inflammatory and atherogenic processes of elderly subjects, but also shows that PBMC gene expression profiles can be used to show effects of nutrition on human health status. Fasting venous blood samples were collected at baseline and after 26 weeks of supplementation with either 1.8 g EPA and DHA or HOSF. 4 ml blood was collected for PBMC isolation, using BD Vacutainer Cell Preparation Tubes with sodium citrate (BD, Breda, The Netherlands). Immediately after blood collection PBMCs were isolated according to the manufacturerâs manual. PBMC RNA was isolated from all PBMC samples using Qiagen RNeasy Micro kit (Qiagen, Venlo, the Netherlands). Total RNA from PBMCs from 48 subjects was labeled using a one-cycle cDNA labeling kit (MessageAmpTM II-Biotin Enhanced Kit, Ambion, Inc.) and hybridized to custom designed NuGO GeneChip arrays.

Dataset Information

Transcription profiling of blood cells from hypertriglyceridemic men treated with docosahexaenoic acid shows suppression of LDLR and OLR1 gene expression.

Publications

Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men.

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