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

J Intern Med. 2014 Nov;276(5):498-511. doi: 10.1111/joim.12217. Epub 2014 Mar 20.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01034423.

Keywords: fish oil; intervention; n-3 fatty acid; peripheral blood mononuclear cells; transcriptome.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis / physiology*
  • Cell Cycle / physiology*
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage*
  • Double-Blind Method
  • Eicosapentaenoic Acid / administration & dosage*
  • Endoplasmic Reticulum Stress / physiology*
  • Female
  • Gene Expression Profiling*
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Tissue Array Analysis
  • Young Adult

Substances

  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid

Associated data

  • ClinicalTrials.gov/NCT01034423