Fish oil supplementation induces expression of genes related to cell cycle, endoplasmic reticulum stress and apoptosis in peripheral blood mononuclear cells: a transcriptomic approach

BACKGROUND Fish oil supplementation has been shown to alter gene expression of mononuclear cells both in vitro and in vivo. However, little is known about the total transcriptome profile in healthy subjects after intake of fish oil. We therefore investigated the gene expression profile in peripheral blood mononuclear cells (PBMCs) after intake of fish oil for 7 weeks using transcriptome analyses. DESIGN In a 7-week, double-blinded, randomized, controlled, parallel-group study, healthy subjects received 8 g day(-1) fish oil (1.6 g day(-1) eicosapentaenoic acid + docosahexaenoic acid) (n = 17) or 8 g day(-1) high oleic sunflower oil (n = 19). Microarray analyses of RNA isolated from PBMCs were performed at baseline and after 7 weeks of intervention. RESULTS Cell cycle, DNA packaging and chromosome organization are biological processes found to be upregulated after intake of fish oil compared to high oleic sunflower oil using a moderated t-test. In addition, gene set enrichment analysis identified several enriched gene sets after intake of fish oil. The genes contributing to the significantly different gene sets in the subjects given fish oil compared with the control group are involved in cell cycle, endoplasmic reticulum (ER) stress and apoptosis. Gene transcripts with common motifs for 35 known transcription factors including E2F, TP53 and ATF4 were upregulated after intake of fish oil. CONCLUSION We have shown that intake of fish oil for 7 weeks modulates gene expression in PBMCs of healthy subjects. The increased expression of genes related to cell cycle, ER stress and apoptosis suggests that intake of fish oil may modulate basic cellular processes involved in normal cellular function.