Abstract
Background
Health benefits from low n-6:n-3 fatty acid (FA) ratio on cardiovascular risk have been shown. However, the impact of the source of n-3 FAs has not been fully investigated.
Aim
Our purpose was to investigate cardiovascular benefits of oils with a low ratio of n-6:n-3 FAs, but different sources of n-3 FAs in C57BL/6 mice.
Methods
Twenty-one mice were divided into 3 groups (n = 7) and fed a diet supplemented with either a fish or flaxseed oil-based ‘designer oils’ with an approximate n-6:n-3 FA ratio of 2/1 or with a safflower-oil-based diet with a ratio of 25/1, for 16 weeks. Plasma lipids and fatty acid profile of the liver tissue were characterized.
Results
Compared to baseline, plasma triacylglycerol levels declined (>50%) in all groups by week 4. Plasma cholesterol levels were reduced in both fish and flax groups by 27% and 36%, respectively, as compared to controls at endpoint. The levels of EPA and DHA in liver phospholipids were significantly increased in both fish and flax groups as compared to the control group, with more profound increases in the fish group. Arachidonic acid levels were similarly decreased in the liver tissues from both fish and flax groups as compared to controls.
Conclusions
Our data suggest that health benefits may be achieved by lowering dietary n-6:n-3 FA even in a high fat diet medium.
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References
Abedin L, Lien EL, Vingrys AJ, Sinclair AJ (1999) The effects of dietary alpha-linolenic acid compared with docosahexaenoic acid on brain, retina, liver, and heart in the guinea pig. Lipids 34:475–482
Alwayn IP, Andersson C, Zauscher B, Gura K, Nose V, Puder M (2005) Omega-3 fatty acids improve hepatic steatosis in a murine model: potential implications for the marginal steatotic liver donor. Transplantation 79:606–608
Ander BP, Weber AR, Rampersad PP, Gilchrist JS, Pierce GN, Lukas A (2004) Dietary flaxseed protects against ventricular fibrillation induced by ischemia-reperfusion in normal and hypercholesterolemic rabbits. J Nutr 134:3250–3256
Barcelli UO, Beach DC, Pollak VE (1988) The influence of n-6 and n-3 fatty acids on kidney phospholipids composition and on eicosanoid production in aging rats. Lipids 23:309–312
Barcelo-Coblijn G, Collison LW, Jolly CA, Murphy EJ (2005) Dietary α-linolenic acid increases brain but not heart and liver docosahexaenoic acid levels. Lipids 40:787–798
Brenner RR (1974) The oxidative desaturation of unsaturated fatty acids in animals. Mol Cell Biochem 3:41–52
Calabresi L, Villa N, Canavesi M, Sirtori CR, James RW, Bernini F et al (2004) An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia. Metabolism 53:153–158
Chrysohoou C, Panagiotakos DB, Pitsavos C, Skoumas J, Krinos X, Chloptsios Y, Nikolaou V, Stefanadis C (2007) Long-term fish consumption is associated with protection against arrhythmia in healthy persons in a Mediterranean region—the ATTICA study. Am J Clin Nutr 85:1385–1391
Du C, Sato A, Watanabe S, Wu C, Ikemoto A, Ando K, Kikugawa K, Fujii Y, Okuyama H (2003) Cholesterol synthesis in mice is suppressed but lipofuscin formation is not affected by long-term feeding of n-3 fatty acid-enriched oils compared with lard and n-6 fatty acid-enriched oils. Biol Pharm Bull 26:766–770
Culp BR, Lands WE, Lucches BR, Pitt B, Romson J (1980) The effect of dietary supplementation of fish oil on experimental myocardial infarction. Prostaglandins 20:1021–1031
Davidson MH (2006) Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. Am J Cardiol 98:27i–33i
Djousse L, Pankow JS, Eckfeldt JH, Folsom AR, Hopkins PN, Province MA, Hong Y, Ellison RC (2001) Relation between dietary linolenic acid and coronary artery disease in the National Heart, Lung, and Blood Institute Family Heart Study. Am J Clin Nutr 74:612–619
Dupasquier CM, Weber AM, Ander BP, Rampersad PP, Steigerwald S, Wigle JT, Mitchell RW, Kroeger EA, Gilchrest JS, Moghadasian MM, Lukas A, Pierce GN (2006) Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits. Am J Physiol Heart Circ Physiol 291:H2987–H2996
Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC et al (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 320:265–271
Folch J, Les M, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animals. J Biol Chem 226:497–509
Fritsche KL, Byrge M, Feng C (1999) Dietary omega-3 polyunsaturated fatty acids from fish oil reduce interleukin-12 and interferon-gamma production in mice. Immunol Lett 65:167–173
Gallai V, Sarchielli P, Trequattrini A, Franceschini M, Floridi A, Firenzi C, Alberti A, Di Benedetto D, Stragliotto E (1995) Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol 56:143–153
Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ (2002). Blood pressure response to fish oil supplementation: meta-regression analysis of randomized trial. J Hypertens 20:1493–1499
Gerster H (1998) Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? Int J Vitam Nutr Res 68:159–173
Goyens PL, Mensink RP (2005) The dietary alpha-linolenic acid to linoleic acid ratio does not affect the serum lipoprotein profile in humans. J Nutr 135:2799–804
Harper CR, Edwards MJ, DeFilipis AP, Jacobson TA (2006) Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans. J Nutr 136:83–87
Harris WS, Bulchandani D (2006) Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol 17:387–393
Hu FB, Bronner L, Willett WC, Stampfer MJ, Rexrode KM, Albert CM, Hunter D, Manson JE (2002) Fish and omega-3 fatty aicd intake and risk of coronary heart disease in women. JAMA 287:1815–1821
Ishida BY, Blanche PJ, Nichols AV, Yasher M, Paigen B (1991) Effects of atherogenic diet consumption on lipoproteins in mouse strains C57BL/6 and C3H. J Lipid Res 32:559–568
James MJ, Gibson RA, Cleland LG (2000) Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr 71(suppl):343S–348S
Kudo N, Kawashima Y (1997) Fish oil-feeding prevents perfluorooctanoic acid-induced fatty liver in mice. Toxicol Appl Pharmacol 145:285–293
Maki KC, Van Elswyk ME, McCarthy D, Seeley MA, Veith PE, Hess SP, Ingram KA, Halvorson JJ, Calaguas EM, Davidson MH (2003) Lipid responses in mildly hypertriglyceridemic men and women to consumption of docosahexaenoic acid-enriched eggs. Int J Vitam Nutr Res 73:357–368
McLennan PL (1993) Relative effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on cardiac arrhythmias in rats. Am J Clin Nutr 57:207–212
McLennan PL, Abeywardena MY, Charnock JS (1988) Dietary fish oil prevents ventricular fibrillation following coronary artery occlusion and reperfusion. Am Heart J 116:709–717
McLennan PL, Bridle TM, Abeywardena MY, Charnock JS (1993) Comparative efficacy of n-3 and n-6 polyunsaturated fatty acids in modulating ventricular fibrillation threshold in marmoset monkeys. Am J Clin Nutr 58:666–669
Moghadasian MH, McManus BM, Pritchard PH, Frohlich JJ (1997) “Tall oil”-derived phytosterols reduce atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 17:119–126
Mori TA, Burke V, Puddey IB, Watts GF, O’Neal DN, Best JD, Beilin LJ (2000) Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 71:1085–1094
Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, Gillum M, Shulman GI (2006) Fish oil regulates adiponectin secretion by a peroxisome proliferators-activated receptor-gamma-dependent mechanism in mice. Diabetes 55:924–928
Owen AJ, Peter-Przyborowska BA, Hoy AJ, McLennan PL (2004) Dietary fish oil dose- and time-response effects on cardiac phospholipid fatty acid composition. Lipids 39:955–961
Park EJ, Suh M, Ramanujam K, Steiner K, Begg D, Clandinin MT (2005) Diet-induced changes in membrane gangliosides in rat intestinal mucosa, plasma and brain. J Pediatr Gastroenterol Nutr 40:487–495
Simopoulos AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56:365–379
Simopoulos AP (1999) Essential fatty acids in health and chronic disease. Am J Clin Nutr 70(suppl):560S–569S
Suh M, Wierzbicki AA, Clandinin MT (1994) Dietary fat alters membrane composition in rod outer segments in normal and diabetic rats: impact on content of very-long-chain (C ≥ 24) polyenoic fatty acids. Biochim Biophys Acta 1214:54–62
Wang S, Wu D, Matthan N, Lichtenstein A (2007) The impact of different ratios of omega-6 polyunsaturated fatty acids to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) on atherosclerotic lesion formation and inflammatory factors in the LDL receptor knockout (LDLr-/-) mouse. FASEB J 21:231.1
Xu Z, Riediger N, Innis S, Moghadasian MH (2007) Fish oil significantly alters fatty acid profiles in various lipid fractions but not atherogenesis in apo E-KO mice. Eur J Nutr (Epub ahead of print)
Yamashita T, Oda E, Sano T, Yamashita T, Ijiru Y, Giddings JC, Yamamoto J (2005) Varying the ratio of dietary n-6:n-3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse. Thromb Res 116:393–401
Yamazaki T, Nakamori A, Sasaki E, Wada S, Ezaki O (2007) Fish oil prevents sucrose-induced fatty liver but exacerbates high-safflower oil-induced fatty liver in ddy mice. Hepatology 46:1779–1790
Zhao G, Etherton TD, Martin KR, West SG, Gillies PJ, Kris-Etherton PM (2004) Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr 134:2991–2997
Acknowledgments
NR is a recipient of an NSERC Graduate Scholarship. We would also like to thank Krystal Merrells and Amy Kroeker for their technical support. We acknowledge the support of the St. Boniface Hospital and Research Foundation as well.
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Sources of financial support: Natural Sciences and Engineering Research Council of Canada, Heart and Stroke Foundation
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Riediger, N.D., Othman, R., Fitz, E. et al. Low n-6:n-3 fatty acid ratio, with fish- or flaxseed oil, in a high fat diet improves plasma lipids and beneficially alters tissue fatty acid composition in mice. Eur J Nutr 47, 153–160 (2008). https://doi.org/10.1007/s00394-008-0709-8
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DOI: https://doi.org/10.1007/s00394-008-0709-8