Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study.
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.
Hugh Sinclair Unit of Human Nutrition, Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK.
Athanasios
A
Koutsos
Hugh Sinclair Unit of Human Nutrition, Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK.
Kim G
KG
Jackson
Hugh Sinclair Unit of Human Nutrition, Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK.
Stacey
S
Lockyer
Hugh Sinclair Unit of Human Nutrition, Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK.
Andrew
A
Carvalho-Wells
Hugh Sinclair Unit of Human Nutrition, Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK.
Anne M
AM
Minihane
Hugh Sinclair Unit of Human Nutrition, Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK. Electronic address: j.a.lovegrove@reading.ac.uk.
Julie A
JA
Lovegrove
D053318:Apolipoprotein E3 / Q000097:blood / Q000235:genetics; D053327:Apolipoprotein E4 / Q000097:blood / Q000235:genetics; D002318:Cardiovascular Diseases; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008055:Lipids / Q000008:administration & dosage / Q000097:blood; D008070:Lipopolysaccharides; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; C508606:CXCL8 protein, human; D016207:Cytokines; D004041:Dietary Fats; C508609:IL10 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008055:Lipids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004281:Docosahexaenoic Acids
APOE; DHA; Dietary fat manipulation; IL-10; TNF-α