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Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men
Kevin Dawson1, Ling Zhao, Yuriko Adkins
1Center of Excellence in Nutritional Genomics, University of California Davis, Davis, CA 95616, USA.
Insights
Docosahexaenoic acid (DHA) supplementation in men with high triglycerides reduced cardiovascular disease risk factors. DHA suppressed inflammatory gene expression, including LDL receptor and cathepsin L1, offering new insights into its anti-inflammatory mechanisms.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Nutritional Science
Background:
- Docosahexaenoic acid (DHA) supplementation previously reduced cardiovascular disease risk factors in hypertriglyceridemic men.
- Inflammatory markers were among the risk factors positively impacted by DHA.
Purpose of the Study:
- To investigate the global gene expression patterns influenced by DHA supplementation.
- To identify specific genes regulated by DHA in the context of inflammation and cardiovascular risk.
Main Methods:
- Affymetrix GeneChip microarray analysis was performed on blood cells from hypertriglyceridemic men before and after DHA supplementation.
- Blood cells were treated with lipopolysaccharide (LPS) or vehicle to simulate inflammatory conditions.
- Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate differential gene expression.
Main Results:
- DHA supplementation significantly suppressed the expression of low-density lipoprotein (LDL) receptor and cathepsin L1, both induced by LPS.
- DHA also suppressed oxidized LDL receptor 1 (OLR1) expression, although LPS did not induce it.
- Gene Ontology analysis revealed inverse regulation of genes related to immunity, host defense, and inflammatory responses by LPS and DHA.
Conclusions:
- DHA supplementation demonstrates anti-inflammatory effects by modulating gene expression patterns.
- This study identified novel genes regulated by DHA that are associated with cardiovascular disease risk factors.
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.
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