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

ABSTRACT: The hypothesis was that 6 months of dietary n-3 FA supplementation to humans affected expression of genes that might be of significance for inflammatory processes and for Alzheimer´s disease. Effects on global gene expression profiles (Affymetrix Human Focus array) in human blood mononuclear leukocytes obtained from 11 patients with Alzheimer´s disease before and after 6 months of a DHA-rich n-3 fatty acid supplementation. Data analyses were performed using Gene chip Operating Software (GCOS) Version 1.4. Two Samples, GSM735991 and GSM736014, are missing CEL files due to storage failure.

ORGANISM(S): Homo sapiens

SUBMITTER: Inger Vedin

PROVIDER: E-GEOD-29680 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Vedin Inger I Cederholm Tommy T Freund-Levi Yvonne Y Basun Hans H Garlind Anita A Irving Gerd Faxén GF Eriksdotter-Jönhagen Maria M Wahlund Lars-Olof LO Dahlman Ingrid I Palmblad Jan J

PloS one 20120424 4

<h4>Background</h4>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 bloo ...[more]

PMID: 22545106

Similar Datasets

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

Project description:The hypothesis was that 6 months of dietary n-3 FA supplementation to humans affected expression of genes that might be of significance for inflammatory processes and for Alzheimer´s disease.

2012-05-24 | GSE29680 | GEO

DNA methylation changes in blood leukocytes following an omega-3 fatty acid supplementation

Project description:The objective is to investigate, using genome-wide DNA methylation analyses, methylation changes following an n-3 FA supplementation in overweight and obese subjects and to identify specific biological pathways potentially altered by the supplementation.

2017-04-22 | GSE98056 | GEO

DHA supplementation suppresses LDLR and OLR1 gene expression in blood cells from hypertriglyceridemic men

Project description: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.

2010-01-30 | GSE20114 | GEO

Effect of prenatal DHA supplementation on the infant epigenome

Project description:Evidence is accumulating that nutritional exposures in utero can influence health outcomes in later life. Animal studies and human epidemiological studies have implicated epigenetic modifications as playing a key role in this process, but there are limited data from large well-controlled human intervention trials. This study utilised a large double-blind randomized placebo-controlled trial to test whether a defined nutritional exposure in utero, in this case docosahexaenoic acid (DHA), could alter the infant epigenome. Pregnant mothers consumed DHA-rich fish oil (800 mg DHA/d) or placebo supplements from 20 weeks’ gestation to delivery. Blood spots were collected from the children at birth (n=991) and blood leukocytes at 5 years (n=667). Global DNA methylation was measured in all samples and Illumina HumanMethylation450K BeadChip arrays were used for genome-wide methylation profiling in a subset of 369 children at birth and 65 children at 5 years. There were no differences in global DNA methylation levels between the DHA and control group either at birth or at 5 years, but we identified 21 differentially methylated regions (DMRs) at birth, showing small DNA methylation differences (<5%) between the treatment groups, some of which seemed to persist until 5 years. The number of DMRs at birth was greater in males (127 DMRs) and in females (72 DMRs) separately, indicating a gender-specific effect. In conclusion, maternal DHA supplementation during the second half of pregnancy had small effects on DNA methylation of infants. While the potential functional significance of these changes remains to be determined, these findings further support the role of epigenetic modifications in developmental programming in humans, and points the way for future studies.

2018-02-06 | GSE89278 | GEO

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

Project description: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.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.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.ClinicalTrials.gov NCT00211159.

| S-EPMC3335851 | biostudies-literature

Inflammation associated gene expression in the mammary gland of lactating mothers who delivered preterm and were randomly assigned to DHA supplementation.

Project description:Background: This is a transcriptome analysis of specimens obtained from a randomized trial of lactating mothers assigned to 200mg/day DHA, STD or 1000mg/day DHA, EXP. Methods: High quality extracellular mammary epithelial cell mRNA was isolated from fresh milk fat and submitted for RNA-sequencing in n=6 EXP and n=4 STD samples. Results: There were 409 DEG. In the EXP group, up-regulation of inflammation-inbibiting genes was seen and down-regulation of pro-inflammatory genes. Ontological analysis revealed 5 clusters of up-regulated gene sets in the EXP group, including immune regulation and management of oxidative stress associated clusters. Conclusion: Findings reveal that increased DHA supplementation during lactation can modulate the expression of inflammation-associated genes within the mammary gland.

2022-06-15 | GSE181990 | GEO

LDLR-/- mice aorte: Control vs DHA

Project description:The omega-3 fatty acid docosahexaenoic acid (DHA) has potent anti-atherogenic properties but its mechanisms of action at the vascular level remain poorly explored. Knowing the broad range of molecular targets of omega-3 fatty acids, microarray analysis was used to open-mindedly evaluate the effects of DHA on aorta gene expression in LDLR-/- mice and better understand its local anti-atherogenic action . Mice were fed an atherogenic diet and received daily oral gavages with oils rich in oleic acid or DHA. Bioinformatics analysis of microarray data first identified inflammation and innate immunity as processes the most affected by DHA supplementation within aorta. More precisely, several down-regulated genes were associated with the inflammatory functions of macrophages (e.g. CCL5, CCR7), cell movement (e.g. ICAM-2, SELP, PECAM-1), and the major histocompatibility complex (e.g. HLA-DQA1, HLA-DRB1). Interestingly, the expression of several genes were identified as specifc biomarkers of macrophage polarization and their changes suggested a preferential orientation towards a M2 reparative phenotype. This observation was supported by the upstream regulator analysis highlighting the involvment of three main regulators of macrophage polarization, namely PPARM-NM-3 (z-score=2.367, p=1.50x10-13), INFM-NM-3 (z-score=-2.797, p=2.81x10-14) and NFM-NM-:B (z-score=2.360, p=6.32x10-9). Moreover, immunohistological analysis of aortic root revealed an increased abundance of Arg1 (+111%, p=0.01), a specific biomarker of M2 macrophage.The present study showed for the first time that DHA supplementation during atherogenesis is associated with protective modulation of inflammation and innate immunity pathways within aorta putatively through the orientation of plaque macrophages towards a M2 reparative phenotype. Mice (LDLR-/-) Aorta samples. 2 groups: Control (K), DHA (C). Biological replicates=8. Dye switch.

2015-01-10 | E-GEOD-59661 | biostudies-arrayexpress

The jejunal proteomic study to investigate the underlying biological effects of maternal DHA supplementation during lactation on intestinal development of weaning pups in early life by using a mice model.

Project description:Docosahexaenoic acid (DHA) is well known to promote visual and brain development while its protective effect on intestinal development in early life remains unknown. In order to understand the underlying biological effects of maternal DHA supplementation during lactation on the intestinal development of pups, we analyzed the proteomics of jejunum tissues from three groups with the DIA-MS method.

2024-06-27 | PXD052063 | Pride

Genome-wide analysis of hepatic gene expression in patients with non-alcoholic steatohepatitis (NASH) before and after 1 year supplementation with n-3 polyunsaturated fatty acids (PUFA) from fishoil

Project description:Fishoil or n-3 PUFA supplementation has shown some beneficial effects in patients with NASH. It is known that n-3 PUFA can influence hepatic gene expression. However, the effect of n-3 PUFA supplementation on hepatic gene expression has not been examined in patients with NASH. Aim of this pilot study was to examine the effect of n-3 PUFA supplementation on liver n-3 PUFA levels, hepatic gene expression and liver histology in patients with NASH. In a single-arm pilot intervention study, the effect of a one year n-3 PUFA supplementation on hepatic gene expression (Illumina Microarray), liver histology, and liver and erythrocyte PUFA was examined in 11 adult patients with NASH. For the intervention trial, NASH patients received n-3 PUFA supplementation from fish oil (2 g fish oil per day, containing 740-840 mg eicosapentaenoic acid (EPA) and 400-440 mg docosahexaenoic acid (DHA) quantified as ethyl ester) for one year. The supplement was produced by Ocean Nutrition Canada Ltd. (Dartmouth, NS, Canada) (product code 4020PB1000CT, Lots # 21211, 24168, and 31639). The selected supplement was within the range used in previous studies, where doses of n-3 PUFA and the EPA/DHA balance varied widely. Effects of n-3 PUFA on liver steatosis were observed in other studies by ultrasound within 6 to 12 months. To increase safety and acceptance of the second liver biopsy, an intervention period of 12 months was selected. During the intervention, patients were asked to maintain their habitual diet and physical activity. Fishoil supplementation lead to increased n-3 PUFA in erythrocyte total lipids and hepatic lipids. However, there was no significant change in liver histology or hepatic gene expression between baseline and post-intervention.

2019-09-30 | GSE96971 | GEO

LDLR-/- mice aorte: Control vs DHA

Project description:The omega-3 fatty acid docosahexaenoic acid (DHA) has potent anti-atherogenic properties but its mechanisms of action at the vascular level remain poorly explored. Knowing the broad range of molecular targets of omega-3 fatty acids, microarray analysis was used to open-mindedly evaluate the effects of DHA on aorta gene expression in LDLR-/- mice and better understand its local anti-atherogenic action . Mice were fed an atherogenic diet and received daily oral gavages with oils rich in oleic acid or DHA. Bioinformatics analysis of microarray data first identified inflammation and innate immunity as processes the most affected by DHA supplementation within aorta. More precisely, several down-regulated genes were associated with the inflammatory functions of macrophages (e.g. CCL5, CCR7), cell movement (e.g. ICAM-2, SELP, PECAM-1), and the major histocompatibility complex (e.g. HLA-DQA1, HLA-DRB1). Interestingly, the expression of several genes were identified as specifc biomarkers of macrophage polarization and their changes suggested a preferential orientation towards a M2 reparative phenotype. This observation was supported by the upstream regulator analysis highlighting the involvment of three main regulators of macrophage polarization, namely PPARγ (z-score=2.367, p=1.50x10-13), INFγ (z-score=-2.797, p=2.81x10-14) and NFκB (z-score=2.360, p=6.32x10-9). Moreover, immunohistological analysis of aortic root revealed an increased abundance of Arg1 (+111%, p=0.01), a specific biomarker of M2 macrophage.The present study showed for the first time that DHA supplementation during atherogenesis is associated with protective modulation of inflammation and innate immunity pathways within aorta putatively through the orientation of plaque macrophages towards a M2 reparative phenotype.

2015-01-10 | GSE59661 | GEO

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