Effects of fish and krill oil on gene expression in peripheral blood mononuclear cells and circulating markers of inflammation: A randomised controlled trial

Consumption of omega-3 fatty acids and fatty fish is associated with cardioprotective effects, mainly by lowering serum triglycerides and reducing inflammation. Krill oil is a preferred source of omega-3 fatty acids by some because of concerns about fish resources.

The mechanisms underlying the beneficial effects of omega-3 fatty acids are thought to include modification of membrane fatty acids and modulation of gene expression. One way to assess the effects of interventions like fish oil and krill oil is to evaluate gene expression of peripheral blood mononuclear cells (PBMCs).

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Methods

Researchers in Norway conducted an 8-week randomized controlled trial to compare the effects of lean and fatty fish, krill oil, and high-oleic sunflower oil on PBMC expression of genes related to lipid metabolism, glucose metabolism, and inflammation. 

Healthy adults were randomized to consume 3 fish meals per week, 8 krill oil capsules per day (RIMFROST Sublime®), or 8 capsules of sunflower oil with added astaxanthin per day. Weekly intakes of omega-3 fatty acids were 4103 mg in the fish group, 4654 mg in the krill oil group, and 0 mg in the sunflower oil group. Fasting blood samples were drawn at baseline and after 8 weeks to evaluate mRNA expression of 40 genes. 

Results

Thirty-six participants (12 in each group) completed the study. The change in gene expression between the 3 groups was significantly different for 4 genes: PPAR-gamma coactivator 1A (PPARGC1A), stearoyl-CoA desaturase (SCD), ATP binding cassette A1 (ABCA1), and cluster of differentiation 40 (CD40). 

Within-group analysis showed that fish consumption significantly altered expression of only 4 genes. Krill oil significantly altered expression of 13 genes involved in glucose metabolism, cholesterol metabolism, and beta-oxidation. Sunflower oil significantly altered expression of 16 genes involved in inflammation and cholesterol efflux.      

Sunflower oil appears to regulate genes involved in inflammation.

Three of the genes that were downregulated in the krill group (PPARGC1A, PDK4, and SLC25A12) suggested a shift toward glucose utilization and away from gluconeogenesis. Other genes that were downregulated in the krill group (SREBF2, HMGCR, and HMGCS1) suggested a shift in cholesterol metabolism. Other changes in the krill group suggested a decrease in mitochondrial beta-oxidation, which was an unexpected finding.  

This study also evaluated changes in circulating markers of inflammation and endothelial function but found no significant changes in any groups. It might be that the daily intakes of omega-3 fatty acids were too low, or the duration of the study was too short to see anti-inflammatory effects. 

Conclusions

Taken together, the researchers concluded that krill oil and sunflower oil with astaxanthin regulate more genes than fish. Krill oil regulated genes involved in glucose and cholesterol metabolism, whereas sunflower oil regulated genes involved in inflammation. Further research is needed to determine how these changes in gene expression translate into clinical effects.

Rundblad, A., Holven, K.B., Bruheim, I., Myhrstad, M.C., & Ulven, S.M. (2018). Effects of fish and krill oil on gene expression in peripheral blood mononuclear cells and circulating markers of inflammation: A randomised controlled trial. Journal of Nutritional Science, 7, e10.