The PBMC transcriptome profile after intake of oxidized versus high-quality fish oil: an explorative study in healthy subjects

Mari C W Myhrstad, Inger Ottestad, Clara-Cecilie Günther, Einar Ryeng, Marit Holden, Astrid Nilsson, Kirsti W Brønner, Achim Kohler, Grethe I A Borge, Kirsten B Holven, Stine M Ulven, Mari C W Myhrstad, Inger Ottestad, Clara-Cecilie Günther, Einar Ryeng, Marit Holden, Astrid Nilsson, Kirsti W Brønner, Achim Kohler, Grethe I A Borge, Kirsten B Holven, Stine M Ulven

Abstract

Background: Marine long-chain polyunsaturated fatty acids are susceptible to oxidation, generating a range of different oxidation products with suggested negative health effects. The aim of the present study was to utilize sensitive high-throughput transcriptome analyses to investigate potential unfavorable effects of oxidized fish oil (PV: 18 meq/kg; AV: 9) compared to high-quality fish oil (PV: 4 meq/kg; AV: 3).

Methods: In a double-blinded randomized controlled study for seven weeks, 35 healthy subjects were assigned to 8 g of either oxidized fish oil or high quality fish oil. The daily dose of EPA+DHA was 1.6 g. Peripheral blood mononuclear cells were isolated at baseline and after 7 weeks and transcriptome analyses were performed with the illuminaHT-12 v4 Expression BeadChip.

Results: No gene transcripts, biological processes, pathway or network were significantly changed in the oxidized fish oil group compared to the fish oil group. Furthermore, gene sets related to oxidative stress and cardiovascular disease were not differently regulated between the groups. Within group analyses revealed a more prominent effect after intake of high quality fish oil as 11 gene transcripts were significantly (FDR < 0.1) changed from baseline versus three within the oxidized fish oil group.

Conclusion: The suggested concern linking lipid oxidation products to short-term unfavorable health effects may therefore not be evident at a molecular level in this explorative study.

Trial registration: ClinicalTrials.gov, NCT01034423.

Keywords: Human intervention; Oxidized fish oil; PBMCs; Transcriptome; n-3 fatty acids.

Figures

Fig. 1
Fig. 1
Flow chart of the study showing subjects enrolled, lost during follow-up, and number of subjects included in the statistical analysis at the baseline and after 3 weeks of fish oil supplementation. FO group fish oil group, oxFO oxidized fish oil group, HOSO high-oleic sunflower oil group

References

    1. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. 1999 Lancet 354:447-55.
    1. Yokoyama M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369:1090–8. doi: 10.1016/S0140-6736(07)60527-3.
    1. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM. n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr. 2006;83:1526S–35.
    1. Lichtenstein AH, et al. Summary of American Heart Association Diet and Lifestyle Recommendations revision 2006. Arterioscler Thromb Vasc Biol. 2006;26:2186–91. doi: 10.1161/01.ATV.0000238352.25222.5e.
    1. Mozaffarian D. Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death. Am J Clin Nutr. 2008;87:1991S–6.
    1. Catala A. Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and/or pathological conditions. Chem Phys Lipids. 2009;157:1–11. doi: 10.1016/j.chemphyslip.2008.09.004.
    1. Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 1991;11:81–128. doi: 10.1016/0891-5849(91)90192-6.
    1. Siddiqui RA, Harvey K, Stillwell W. Anticancer properties of oxidation products of docosahexaenoic acid. Chem Phys Lipids. 2008;153:47–56. doi: 10.1016/j.chemphyslip.2008.02.009.
    1. (GOED) GOfEaDo-s (2006) Global Organization for EPA and DHA omega-3s (GOED) GOED
    1. (VKM) NSCfFS (2012) Description of the processes in the value chain and risk assessment of decomposition substances and oxidation products in fish oils (08-504-4-final). vol 08-504-4-final.
    1. Albert BB, et al. Fish oil supplements in New Zealand are highly oxidised and do not meet label content of n-3 PUFA. Sci Rep. 2015;5:7928. doi: 10.1038/srep07928.
    1. Halvorsen BL, Blomhoff R. Determination of lipid oxidation products in vegetable oils and marine omega-3 supplements. Food Nutr Res. 2011; 55 doi:10.3402/fnr.v55i0.5792
    1. Kolanowski W. Omega-3 LC PUFA contents and oxidative stability of encapsulated fish oil dietary supplements. Int J Food Prop. 2010;13:498–511. doi: 10.1080/10942910802652222.
    1. (BIOHAZ) EPoBH Scientific opinion on fish oil for human consumption. Food hygiene, including rancidity. EFSA J. 2010;8:48.
    1. Albert BB, Cameron-Smith D, Hofman PL, Cutfield WS. Oxidation of marine omega-3 supplements and human health. Biomed Res Int. 2013;2013:464921. doi: 10.1155/2013/464921.
    1. Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr. 1993;57:715S–24.
    1. Niki E. Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med. 2009;47:469–84. doi: 10.1016/j.freeradbiomed.2009.05.032.
    1. Riahi Y, Cohen G, Shamni O, Sasson S. Signaling and cytotoxic functions of 4-hydroxyalkenals. Am J Physiol Endocrinol Metab. 2010;299:E879–86. doi: 10.1152/ajpendo.00508.2010.
    1. Sayre LM, Lin D, Yuan Q, Zhu X, Tang X. Protein adducts generated from products of lipid oxidation: focus on HNE and one. Drug Metab Rev. 2006;38:651–75. doi: 10.1080/03602530600959508.
    1. Awada M, et al. Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells. J Lipid Res. 2012;53:2069–80. doi: 10.1194/jlr.M026179.
    1. Esterbauer H. Cytotoxicity and genotoxicity of lipid-oxidation products. Am J Clin Nutr. 1993;57:779S–85.
    1. Staprans I, Hardman DA, Pan XM, Feingold KR. Effect of oxidized lipids in the diet on oxidized lipid levels in postprandial serum chylomicrons of diabetic patients. Diabetes Care. 1999;22:300–6. doi: 10.2337/diacare.22.2.300.
    1. Staprans I, Rapp JH, Pan XM, Kim KY, Feingold KR. Oxidized lipids in the diet are a source of oxidized lipid in chylomicrons of human serum. Arterioscler Thromb. 1994;14:1900–5. doi: 10.1161/01.ATV.14.12.1900.
    1. Sutherland WH, de Jong SA, Hessian PA, Williams MJ. Ingestion of native and thermally oxidized polyunsaturated fats acutely increases circulating numbers of endothelial microparticles. Metabolism. 2010;59:446–53. doi: 10.1016/j.metabol.2009.07.033.
    1. Sutherland WH, de Jong SA, Walker RJ, Williams MJ, Murray Skeaff C, Duncan A, Harper M. Effect of meals rich in heated olive and safflower oils on oxidation of postprandial serum in healthy men. Atherosclerosis. 2002;160:195–203.
    1. Wallace AJ, Sutherland WH, Mann JI, Williams SM. The effect of meals rich in thermally stressed olive and safflower oils on postprandial serum paraoxonase activity in patients with diabetes. Eur J Clin Nutr. 2001;55:951–8. doi: 10.1038/sj.ejcn.1601250.
    1. Ottestad I, et al. Intake of oxidised fish oil does not affect circulating levels of oxidised LDL or inflammatory markers in healthy subjects. Nutr Metab Cardiovasc Dis. 2013;23:e3–4. doi: 10.1016/j.numecd.2012.08.009.
    1. Ottestad I et al. Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects: a randomised controlled trial Br J Nutr. 2011:1-12 doi:10.1017/S0007114511005484
    1. Afman L, Milenkovic D, Roche HM. Nutritional aspects of metabolic inflammation in relation to health-insights from transcriptomic biomarkers in PBMC of fatty acids and polyphenols. Mol Nutr Food Res. 2014
    1. de Mello VD, Kolehmanien M, Schwab U, Pulkkinen L, Uusitupa M. Gene expression of peripheral blood mononuclear cells as a tool in dietary intervention studies: what do we know so far? Mol Nutr Food Res. 2012;56:1160–72. doi: 10.1002/mnfr.201100685.
    1. Bouwens M, et al. Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr. 2009;90:415–24. doi: 10.3945/ajcn.2009.27680.
    1. de Mello VD, et al. The effect of fatty or lean fish intake on inflammatory gene expression in peripheral blood mononuclear cells of patients with coronary heart disease. Eur J Nutr. 2009;48:447–55. doi: 10.1007/s00394-009-0033-y.
    1. Kolehmainen M, et al. Bilberries reduce low-grade inflammation in individuals with features of metabolic syndrome. Mol Nutr Food Res. 2012;56:1501–10. doi: 10.1002/mnfr.201200195.
    1. Radler U, et al. A combination of (omega-3) polyunsaturated fatty acids, polyphenols and L-carnitine reduces the plasma lipid levels and increases the expression of genes involved in fatty acid oxidation in human peripheral blood mononuclear cells and HepG2 cells. Ann Nutr Metab. 2011;58:133–40. doi: 10.1159/000327150.
    1. van Dijk SJ, Feskens EJ, Bos MB, de Groot LC, de Vries JH, Muller M, Afman LA. Consumption of a high monounsaturated fat diet reduces oxidative phosphorylation gene expression in peripheral blood mononuclear cells of abdominally overweight men and women. J Nutr. 2012;142:1219–25. doi: 10.3945/jn.111.155283.
    1. Myhrstad MC, et al. 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;276:498–511. doi: 10.1111/joim.12217.
    1. Smyth GK. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004;3:Article3.
    1. Brazma A, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001;29:365–71. doi: 10.1038/ng1201-365.
    1. Allen RG, Tresini M. Oxidative stress and gene regulation. Free Radic Biol Med. 2000;28:463–99. doi: 10.1016/S0891-5849(99)00242-7.
    1. Mathai JP, Germain M, Shore GC. BH3-only BIK regulates BAX, BAK-dependent release of Ca2+ from endoplasmic reticulum stores and mitochondrial apoptosis during stress-induced cell death. J Biol Chem. 2005;280:23829–36. doi: 10.1074/jbc.M500800200.
    1. Zhang T, Walensky LD, Saghatelian A. A nonapoptotic role for BAX and BAK in eicosanoid metabolism. ACS Chem Biol. 2015;10:1398–403. doi: 10.1021/acschembio.5b00168.
    1. Schmidt S, Stahl F, Mutz KO, Scheper T, Hahn A, Schuchardt JP. Different gene expression profiles in normo- and dyslipidemic men after fish oil supplementation: results from a randomized controlled trial. Lipids Health Dis. 2012a 11:105 doi:10.1186/1476-511X-11-105
    1. Schmidt S, Stahl F, Mutz KO, Scheper T, Hahn A, Schuchardt JP. Transcriptome-based identification of antioxidative gene expression after fish oil supplementation in normo- and dyslipidemic men. Nutr Metab 2012b 9:45 doi:10.1186/1743-7075-9-45
    1. Vedin I, et al. Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood mononuclear leukocytes: the OmegAD study. PLoS One. 2012;7:e35425. doi: 10.1371/journal.pone.0035425.
    1. Kostner KM. Activation of the complement system: a crucial link between inflammation and atherosclerosis? Eur J Clin Invest. 2004;34:800–2. doi: 10.1111/j.1365-2362.2004.01431.x.
    1. Lewis RD, Perry MJ, Guschina IA, Jackson CL, Morgan BP, Hughes TR. CD55 deficiency protects against atherosclerosis in ApoE-deficient mice via C3a modulation of lipid metabolism. Am J Pathol. 2011;179:1601–7. doi: 10.1016/j.ajpath.2011.06.015.
    1. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308:1024–33. doi: 10.1001/2012.jama.11374.
    1. Garcia-Hernandez VM, Gallar M, Sanchez-Soriano J, Micol V, Roche E, Garcia-Garcia E. Effect of omega-3 dietary supplements with different oxidation levels in the lipidic profile of women: a randomized controlled trial. Int J Food Sci Nutr. 2013;64:993–1000. doi: 10.3109/09637486.2013.812619.

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