Transcriptome-based identification of antioxidative gene expression after fish oil supplementation in normo- and dyslipidemic men

Simone Schmidt, Frank Stahl, Kai-Oliver Mutz, Thomas Scheper, Andreas Hahn, Jan Philipp Schuchardt, Simone Schmidt, Frank Stahl, Kai-Oliver Mutz, Thomas Scheper, Andreas Hahn, Jan Philipp Schuchardt

Abstract

Background: The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), especially in dyslipidemic subjects with a high risk of cardiovascular disease, are widely described in the literature. A lot of effects of n-3 PUFAs and their oxidized metabolites are triggered by regulating the expression of genes. Currently, it is uncertain if the administration of n-3 PUFAs results in different expression changes of genes related to antioxidative mechanisms in normo- and dyslipidemic subjects, which may partly explain their cardioprotective effects. The aim of this study was to investigate the effects of n-3 PUFA supplementation on expression changes of genes involved in oxidative processes.

Methods: Ten normo- and ten dyslipidemic men were supplemented for twelve weeks with fish oil capsules, providing 1.14 g docosahexaenoic acid and 1.56 g eicosapentaenoic acid. Gene expression levels were determined by whole genome microarray analysis and quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Using microarrays, we discovered an increased expression of antioxidative enzymes and a decreased expression of pro-oxidative and tissue enzymes, such as cytochrome P450 enzymes and matrix metalloproteinases, in both normo- and dyslipidemic men. An up-regulation of catalase and heme oxigenase 2 in both normo- and dyslipidemic subjects and an up-regulation of cytochrome P450 enzyme 1A2 only in dyslipidemic subjects could be observed by qRT-PCR analysis.

Conclusions: Supplementation of normo- and dyslipidemic subjects with n-3 PUFAs changed the expression of genes related to oxidative processes, which may suggest antioxidative and potential cardioprotective effects of n-3 PUFAs. Further studies combining genetic and metabolic endpoints are needed to verify the regulative effects of n-3 PUFAs in antioxidative gene expression to better understand their beneficial effects in health and disease prevention.

Trial registration: ClinicalTrials.gov (ID: NCT01089231).

Figures

Figure 1
Figure 1
Transcript levels of target genes in normo- and dyslipidemic men. Transcript levels of catalase (CAT), heme oxygenase 2 (HMOX2) and cytochrome P450 enzyme 1 A2 (CYP1A2) was determined by qRT-PCR in normo- and dyslipidemic men before (t0) and after twelve weeks (t12) of fish oil supplementation. Pooled group samples were used in triplicates. Triplicates were averaged and corrected by two reference genes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and ribosomal proteine S2 (RPS2). Corrected expressions were compared with baseline gene expression of normolipidemic subjects and relative expression changes are displayed. Differences between baseline and endpoint (t12) Ct values were tested by a paired t-test and differences between groups at each time point were tested by unpaired t-test.

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