The role of FADS1/2 polymorphisms on cardiometabolic markers and fatty acid profiles in young adults consuming fish oil supplements

Kaitlin Roke, David M Mutch, Kaitlin Roke, David M Mutch

Abstract

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids (FAs) known to influence cardiometabolic markers of health. Evidence suggests that single nucleotide polymorphisms (SNPs) in the fatty acid desaturase 1 and 2 (FADS1/2) gene cluster may influence an individual's response to n-3 FAs. This study examined the impact of a moderate daily dose of EPA and DHA fish oil supplements on cardiometabolic markers, FA levels in serum and red blood cells (RBC), and whether these endpoints were influenced by SNPs in FADS1/2. Young adults consumed fish oil supplements (1.8 g total EPA/DHA per day) for 12 weeks followed by an 8-week washout period. Serum and RBC FA profiles were analyzed every two weeks by gas chromatography. Two SNPs were genotyped: rs174537 in FADS1 and rs174576 in FADS2. Participants had significantly reduced levels of blood triglycerides (-13%) and glucose (-11%) by week 12; however, these benefits were lost during the washout period. EPA and DHA levels increased significantly in serum (+250% and +51%, respectively) and RBCs (+132% and +18%, respectively) within the first two weeks of supplementation and remained elevated throughout the 12-week period. EPA and DHA levels in RBCs only (not serum) remained significantly elevated (+37% and +24%, respectively) after the washout period. Minor allele carriers for both SNPs experienced greater increases in RBC EPA levels during supplementation; suggesting that genetic variation at this locus can influence an individual's response to fish oil supplements.

Figures

Figure 1
Figure 1
Study timeline and experimental design. The supplementation period lasted for 12 weeks and the washout period for 8 weeks (total duration of 20 weeks). Symbols indicate which measurements were taken at each time-point.
Figure 2
Figure 2
Levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) in serum and RBCs. Relative % EPA in (A) serum and (B) RBCs. Relative % DHA in (C) serum and (D) RBCs. Relative % AA in (E) serum and (F) RBCs. FAs are represented as relative % of total FA values. Numbers on the x-axis represent time in weeks, where baseline is indicated by 0. * Indicates p < 0.05 compared to baseline (0).
Figure 3
Figure 3
Eicosapentaenoic acid (EPA) levels in major and minor allele carriers of the rs174537 SNP in FADS1. (A) Differences in relative % EPA in serum between major and minor allele carriers at both baseline (T0) and week 12 (T12) as well as the interaction between genotype × time. (B) Percent changes (i.e., T0 − T12) for serum % EPA in major and minor allele carriers. (C) Differences in relative % EPA in RBCs between major and minor allele carriers at both T0 and T12 as well as the interaction between genotype × time. (D) Percent change (i.e., T0 − T12) for RBC % EPA in major and minor allele carriers. p-Values are listed above each of the comparisons. Major allele carriers (GG) (n =3) and minor allele carriers (GT+ TT) (n = 9). * Indicates p < 0.05.

References

    1. Cordain L., Eaton S.B., Sebastian A., Mann N., Lindeberg S., Watkins B.A., O’Keefe J.H., Brand-Miller J. Origins and evolution of the western diet: Health implications for the 21st century. Am. J. Clin. Nutr. 2005;81:341–354.
    1. Cleland L.G., James M.J., Proudman S.M. Fish oil: What the prescriber needs to know. Arthritis Res. Ther. 2006;8:202. doi: 10.1186/ar1876.
    1. Kris-Etherton P.M., Harris W.S., Appel L.J. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler. Thromb. Vasc. Biol. 2003;23:e20–e30. doi: 10.1161/01.ATV.0000038493.65177.94.
    1. Tur J., Bibiloni M., Sureda A., Pons A. Dietary sources of omega 3 fatty acids: Public health risks and benefits. Br. J. Nutr. 2012;107:S23–S52. doi: 10.1017/S0007114512001456.
    1. Torrejon C., Jung U., Deckelbaum R. n-3 Fatty acids and cardiovascular disease: Actions and molecular mechanisms. Prostaglandins Leukot. Essent. Fatty Acids. 2007;77:319–326. doi: 10.1016/j.plefa.2007.10.014.
    1. Kromhout D., de Goede J. Update on cardiometabolic health effects of ω-3 fatty acids. Curr. Opin. Lipidol. 2014;25:85–90. doi: 10.1097/MOL.0000000000000041.
    1. Lorente-Cebrián S., Costa A.G., Navas-Carretero S., Zabala M., Martínez J.A., Moreno-Aliaga M.J. Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: A review of the evidence. J. Physiol. Biochem. 2013;69:633–651. doi: 10.1007/s13105-013-0265-4.
    1. Balk E.M., Lichtenstein A.H., Chung M., Kupelnick B., Chew P., Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: A systematic review. Atherosclerosis. 2006;189:19–30. doi: 10.1016/j.atherosclerosis.2006.02.012.
    1. Eslick G.D., Howe P.R., Smith C., Priest R., Bensoussan A. Benefits of fish oil supplementation in hyperlipidemia: A systematic review and meta-analysis. Int. J. Cardiol. 2009;136:4–16. doi: 10.1016/j.ijcard.2008.03.092.
    1. Hartweg J., Perera R., Montori V., Dinneen S., Neil H., Farmer A. Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus. Cochrane Database Syst. Rev. 2008;1 doi: 10.1002/14651858.CD003205.pub2.
    1. Karaouzene N., Merzouk H., Aribi M., Merzouk S., Yahia Berrouiguet A., Tessier C., Narce M. Effects of the association of aging and obesity on lipids, lipoproteins and oxidative stress biomarkers: A comparison of older with young men. Nutr. Metab. Cardiovasc. Dis. 2011;21:792–799. doi: 10.1016/j.numecd.2010.02.007.
    1. Janssen I. Influence of age on the relation between waist circumference and cardiometabolic risk markers. Nutr. Metab. Cardiovasc. Dis. 2009;19:163–169. doi: 10.1016/j.numecd.2008.06.013.
    1. Kitson A.P., Stroud C.K., Stark K.D. Elevated production of docosahexaenoic acid in females: Potential molecular mechanisms. Lipids. 2010;45:209–224. doi: 10.1007/s11745-010-3391-6.
    1. Hodson L., Skeaff C.M., Fielding B.A. Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog. Lipid Res. 2008;47:348–380. doi: 10.1016/j.plipres.2008.03.003.
    1. Metherel A., Armstrong J., Patterson A., Stark K. Assessment of blood measures of n-3 polyunsaturated fatty acids with acute fish oil supplementation and washout in men and women. Prostaglandins Leukot. Essent. Fatty Acids. 2009;81:23–29. doi: 10.1016/j.plefa.2009.05.018.
    1. Marangoni F., Angeli M.T., Colli S., Eligini S., Tremoli E., Sirtori C.R., Galli C. Changes of n-3 and n-6 fatty acids in plasma and circulating cells of normal subjects, after prolonged administration of 20:5 (EPA) and 22:6 (DHA) ethyl esters and prolonged washout. Biochem. Biophys. Acta. 1993;1210:55–62. doi: 10.1016/0005-2760(93)90049-F.
    1. Katan M., Deslypere J., van Birgelen A., Penders M., Zegwaard M. Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: An 18-month controlled study. J. Lipid Res. 1997;38:2012–2022.
    1. Cao J., Schwichtenberg K.A., Hanson N.Q., Tsai M.Y. Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin. Chem. 2006;52:2265–2272. doi: 10.1373/clinchem.2006.072322.
    1. Merino D.M., Ma D., Mutch D.M. Genetic variation in lipid desaturases and its impact on the development of human disease. Lipids Health Dis. 2010;9 doi: 10.1186/1476-511X-9-63.
    1. Kwak J.H., Paik J.K., Kim O.Y., Jang Y., Lee S.-H., Ordovas J.M., Lee J.H. FADS gene polymorphisms in Koreans: Association with ω-6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease. Atherosclerosis. 2011;214:94–100. doi: 10.1016/j.atherosclerosis.2010.10.004.
    1. Kröger J., Schulze M.B. Recent insights into the relation of δ5 desaturase and δ6 desaturase activity to the development of type 2 diabetes. Curr. Opin. Lipidol. 2012;23:4–10. doi: 10.1097/MOL.0b013e32834d2dc5.
    1. Simopoulos A.P. Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: Their role in the determination of nutritional requirements and chronic disease risk. Exp. Biol. Med. 2010;235:785–795. doi: 10.1258/ebm.2010.009298.
    1. Lattka E., Illig T., Heinrich J., Koletzko B. Do fads genotypes enhance our knowledge about fatty acid related phenotypes? Clin. Nutr. 2010;29:277–287. doi: 10.1016/j.clnu.2009.11.005.
    1. Roke K., Ralston J.C., Abdelmagid S., Nielsen D.E., Badawi A., El-Sohemy A., Ma D.W., Mutch D.M. Variation in the fads1/2 gene cluster alters plasma n-6 pufa and is weakly associated with hscrp levels in healthy young adults. Prostaglandins Leukot Essent. Fatty Acids. 2013;89:257–263. doi: 10.1016/j.plefa.2013.06.003.
    1. Martinelli N., Girelli D., Malerba G., Guarini P., Illig T., Trabetti E., Sandri M., Friso S., Pizzolo F., Schaeffer L. FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. Am. J. Clin. Nutr. 2008;88:941–949.
    1. Cormier H., Rudkowska I., Paradis A.-M., Thifault E., Garneau V., Lemieux S., Couture P., Vohl M.-C. Association between polymorphisms in the fatty acid desaturase gene cluster and the plasma triacylglycerol response to an n-3 PUFA supplementation. Nutrients. 2012;4:1026–1041. doi: 10.3390/nu4081026.
    1. Gillingham L.G., Harding S.V., Rideout T.C., Yurkova N., Cunnane S.C., Eck P.K., Jones P.J. Dietary oils and FADS1-FADS2 genetic variants modulate [13c] α-linolenic acid metabolism and plasma fatty acid composition. Am. J. Clin. Nutr. 2013;97:195–207. doi: 10.3945/ajcn.112.043117.
    1. Al-Hilal M., AlSaleh A., Maniou Z., Lewis F.J., Hall W.L., Sanders T.A., O’Dell S.D. Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement. J. Lipid Res. 2013;54:542–551. doi: 10.1194/jlr.P032276.
    1. Lawson L.D., Hughes B.G. Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal. Biochem. Biophys. Res. Commun. 1988;156:960–963. doi: 10.1016/S0006-291X(88)80937-9.
    1. Merino D.M., Johnston H., Clarke S., Roke K., Nielsen D., Badawi A., El-Sohemy A., Ma D.W., Mutch D.M. Polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults. Mol. Genet. Metab. 2011;103:171–178. doi: 10.1016/j.ymgme.2011.02.012.
    1. dbSNP Short Genetic Variations. [(accessed on 8 April 2014)]. Available online:
    1. Lattka E., Illig T., Koletzko B., Heinrich J. Genetic variants of the FADS1 FADS2 gene cluster as related to essential fatty acid metabolism. Curr. Opin. Lipidol. 2010;21:64–69. doi: 10.1097/MOL.0b013e3283327ca8.
    1. Tanaka T., Shen J., Abecasis G.R., Kisialiou A., Ordovas J.M., Guralnik J.M., Singleton A., Bandinelli S., Cherubini A., Arnett D. Genome-wide association study of plasma polyunsaturated fatty acids in the inchianti study. PLoS Genet. 2009;5:e1000338. doi: 10.1371/journal.pgen.1000338.
    1. SNAP SNP Annotation and Proxy Search. [(accessed on 14 October 2013)]. Available online: .
    1. Pettersson F.H., Anderson C.A., Clarke G.M., Barrett J.C., Cardon L.R., Morris A.P., Zondervan K.T. Marker selection for genetic case-control association studies. Nat. Protoc. 2009;4:743–752. doi: 10.1038/nprot.2009.38.
    1. Holub B., Mutch D.M., Pierce G.N., Rodriguez-Leyva D., Aliani M., Innis S., Yan W., Lamarche B., Couture P., Ma D.W. Proceedings from the 2013 canadian nutrition society conference on advances in dietary fats and nutrition. Appl. Physiol. Nutr. Metab. 2014 in press.
    1. Leiter L.A., Fitchett D.H., Gilbert R.E., Gupta M., Mancini G., McFarlane P.A., Ross R., Teoh H., Verma S., Anand S. Cardiometabolic risk in canada: A detailed analysis and position paper by the cardiometabolic risk working group. Can. J. Cardiol. 2011;27:e1–e33.
    1. Pereira M.A., Jacobs D.R., Pins J.J., Raatz S.K., Gross M.D., Slavin J.L., Seaquist E.R. Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults. Am. J. Clin. Nutr. 2002;75:848–855.
    1. Harris W.S., Pottala J.V., Sands S.A., Jones P.G. Comparison of the effects of fish and fish-oil capsules on the n-3 fatty acid content of blood cells and plasma phospholipids. Am. J. Clin. Nutr. 2007;86:1621–1625.
    1. Von Schacky C., Fischer S., Weber P.C. Long-term effects of dietary marine omega-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans. J. Clin. Investig. 1985;76:1626. doi: 10.1172/JCI112147.
    1. Adkins Y., Kelley D.S. Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids. J. Nutr. Biochem. 2010;21:781–792. doi: 10.1016/j.jnutbio.2009.12.004.
    1. Pinel A., Morio-Liondore B., Capel F. n-3 Polyunsaturated fatty acids modulate metabolism of insulin-sensitive tissues: Implication for the prevention of type 2 diabetes. J. Physiol. Biochem. 2013;70:1–12.
    1. Zulyniak M.A., Perreault M., Gerling C., Spriet L.L., Mutch D.M. Fish oil supplementation alters circulating eicosanoid concentrations in young healthy men. Metabolism. 2013;62:1107–1113. doi: 10.1016/j.metabol.2013.02.004.
    1. Fekete K., Marosvölgyi T., Jakobik V., Decsi T. Methods of assessment of n-3 long-chain polyunsaturated fatty acid status in humans: A systematic review. Am. J. Clin. Nutr. 2009;89:2070S–2084S. doi: 10.3945/ajcn.2009.27230I.
    1. Barceló-Coblijn G., Murphy E.J., Othman R., Moghadasian M.H., Kashour T., Friel J.K. Flaxseed oil and fish-oil capsule consumption alters human red blood cell n-3 fatty acid composition: A multiple-dosing trial comparing 2 sources of n-3 fatty acid. Am. J. Clin. Nutr. 2008;88:801–809.
    1. Global Lipids Genetics Consortium. Willer C.J., Schmidt E.M., Sengupta S., Peloso G.M., Gustafsson S., Kanoni S., Ganna A., Chen J., Buchkovich M.L., et al. Discovery and refinement of loci associated with lipid levels. Nat. Genet. 2013;45:1274–1283. doi: 10.1038/ng.2797.
    1. Schaeffer L., Gohlke H., Müller M., Heid I.M., Palmer L.J., Kompauer I., Demmelmair H., Illig T., Koletzko B., Heinrich J. Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum. Mol. Genet. 2006;15:1745–1756. doi: 10.1093/hmg/ddl117.
    1. Keenan A.H., Pedersen T.L., Fillaus K., Larson M.K., Shearer G.C., Newman J.W. Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-hufa in healthy volunteers. J. Lipid Res. 2012;53:1662–1669. doi: 10.1194/jlr.P025577.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren