Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production – Insights from the SATgenε study

Athanasios Koutsos,Kim G Jackson,Stacey Lockyer,Andrew Carvalho-Wells,Anne M Minihane,Julie A Lovegrove

doi:10.1016/j.cyto.2013.12.015

Abstract

Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects.

Highlights

IntroductionThe most widely researched common gene variants, with respect to cardiovascular disease (CVD) risk are the apolipoprotein E (APOE) single nucleotide polymorphisms (SNP) [2]
A subset of the normolipidaemic participants from the SATgene study (n = 52/88), who were prospectively recruited according to apolipoprotein E (APOE) genotype (n = 26 E3/E3 and n = 26 E3/E4) provided blood samples at the beginning of the study and eight weeks after the low fat (LF), high saturated fat (HSF) and HSF with 3.45 g/day docosahexaenoic acid (DHA) (HSF-DHA) diet for the determination of ex vivo cytokine production using whole blood culture
The present study investigated the impact of APOE genotype on the ex vivo cytokine response of normolipidaemic subjects to chronic dietary fat manipulation

Summary

Introduction

The most widely researched common gene variants, with respect to CVD risk are the apolipoprotein E (APOE) single nucleotide polymorphisms (SNP) [2]. The literature is not fully consistent [3,4] APOE4 carriers (approximately 25% of the Caucasian population), have been reported to have a higher risk of CVD. This was originally attributed to elevated blood lipid levels in this subgroup [4]. The mechanisms that relate APOE4 to increased CVD risk may be more complex than solely a lipid effect [1,2] with studies largely conducted in transgenic animals or cell lines indicating that the APOE4 allele is related to a more pro-oxidative and pro-inflammatory state compared with the APOE3 allele [1,2]

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