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

Amanda Rundblad,Mari C Myhrstad,Stine M Ulven,Kirsten B Holven,Inge Bruheim

doi:10.1017/jns.2018.2

Abstract

Marine n-3 (omega-3) fatty acids alter gene expression by regulating the activity of transcription factors. Krill oil is a source of marine n-3 fatty acids that has been shown to modulate gene expression in animal studies; however, the effect in humans is not known. Hence, we aimed to compare the effect of intake of krill oil, lean and fatty fish with a similar content of n-3 fatty acids, and high-oleic sunflower oil (HOSO) with added astaxanthin on the expression of genes involved in glucose and lipid metabolism and inflammation in peripheral blood mononuclear cells (PBMC) as well as circulating inflammatory markers. In an 8-week trial, healthy men and women aged 18-70 years with fasting TAG of 1·3-4·0 mmol/l were randomised to receive krill oil capsules (n 12), HOSO capsules (n 12) or lean and fatty fish (n 12). The weekly intakes of marine n-3 fatty acids from the interventions were 4654, 0 and 4103 mg, respectively. The mRNA expression of four genes, PPAR γ coactivator 1A (PPARGC1A), steaoryl-CoA desaturase (SCD), ATP binding cassette A1 (ABCA1) and cluster of differentiation 40 (CD40), were differently altered by the interventions. Furthermore, within-group analyses revealed that krill oil down-regulated the mRNA expression of thirteen genes, including genes involved in glucose and cholesterol metabolism and β-oxidation. Fish altered the mRNA expression of four genes and HOSO down-regulated sixteen genes, including several inflammation-related genes. There were no differences between the groups in circulating inflammatory markers after the intervention. In conclusion, the intake of krill oil and HOSO with added astaxanthin alter the PBMC mRNA expression of more genes than the intake of fish.

Highlights

Marine n-3 fatty acids alter gene expression by regulating the activity of transcription factors
Krill oil may reduce TAG, especially in subjects with elevated TAG, more human studies are needed to clarify if the effects of krill oil on lipid metabolism differ from the effects of fish and fish oil[7,14,15,16,17,18,19]
We showed that intake of krill oil reduced fasting glucose and that intake of lean and fatty fish increased vitamin D levels, while plasma levels of marine n-3 fatty acids increased in both groups receiving n-3 fatty acids[18]

Summary

Introduction

Marine n-3 (omega-3) fatty acids alter gene expression by regulating the activity of transcription factors. Krill oil may reduce TAG, especially in subjects with elevated TAG, more human studies are needed to clarify if the effects of krill oil on lipid metabolism differ from the effects of fish and fish oil[7,14,15,16,17,18,19] Another beneficial effect of n-3 fatty acids is their ability to reduce levels of circulating inflammatory markers, such as TNFα, IL-1β, IL-6 and IL-8 and intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in various patient groups; the effect in healthy humans and individuals with a high CVD risk is less clear[20,21]. N-3 fatty acids act anti-inflammatory by binding directly to the

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