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Desaturases of fatty acids (FADS) and their physiological and clinical implication


Authors: prof. MUDr. DrSc. Aleš Žák;  prof. MUDr. DrSc. Adolf Slabý;  RNDr. CSc. Eva Tvrzická;  RNDr. Ph.D. Marie Jáchymová;  MUDr. Ph.D. Jaroslav Macášek;  RNDr. Ph.D. Marek Vecka;  doc. MUDr. CSc. Miroslav Zeman;  Mgr. Barbora Staňková
Authors place of work: IV. interní klinika 1. LF UK a VFN, U Nemocnice , Praha , 1 8 1;  Ústav klinické biochemie a laboratorní diagnostiky 1. LF UK a VFN, U Nemocnice 2, Praha 2, 128 2
Published in the journal: Čas. Lék. čes. 2016; 155: 69-75
Category: Review Articles

Summary

States associated with insulin resistance, as overweight/obesity, type 2 diabetes mellitus (DM2), cardiovascular diseases (CVD), some cancers and neuropsychiatric diseases are characterized with a decrease of long-chain polyunsaturated fatty acids (LC-PUFA) levels. Amounts of LC-PUFA depend on the exogenous intake of their precursors [linoleic (LA) and α-linolenic acid (ALA)] and by rate of their metabolism, which is influenced by activities of enzymes, such as Δ6-desaturase (D6D, FADS2), D5D, FADS1, elongases (Elovl2, -5, 6).

Altered activities of D5D/D6D were described in plenty of diseases, e.g. neuropsychiatric (depressive disorders, bipolar disorder, dementia), metabolic (obesity, metabolic syndrome, DM2) and cardiovascular diseases (arterial hypertension, coronary heart disease), inflammatory states and allergy (Crohn’s disease, atopic eczema) or some malignancies. Similar results were obtained in studies dealing with the associations between genotypes/haplotypes of FADS1/FADS2 and above mentioned diseases, or interactions of dietary intake of LA and ALA on one hand and of the polymorphisms of minor allels of FADS1/FADS2, usually characterized by lower activities, on the other hand.

The decrease of the desaturases activities leads to decreased concentrations of products with concomitant increased concentrations of substrates. Associations of some SNP FADS with coronary heart disease, concentrations of plasma lipids, oxidative stress, glucose homeostasis, and inflammatory reaction, were described. Experimental studies on animal models and occurrence of rare diseases, associated with missing or with marked fall activities of D5D/D6D emphasized the significance of desaturases for healthy development of organism as well as for pathogenesis of some disease.

Keywords:
delta-5-desaturase, delta-6-desaturase, genes FADS1/FADS2, polyunsaturated fatty acids, inflammation, oxidative stress, cardiovascular and metabolic diseases


Zdroje

1. Jump DB. Fatty acid regulation of hepatic lipid metabolism. Curr Opin Clin Nutr Metab Care 2011; 14: 115–120.

2. Zdravotnická ročenka České republiky 2009. ÚZIS ČR. URL: uzis.cz

3. Euroaspire III. Euro Heart Survey, Vienna, September 2007. URL: escardio.org

4. Lann D, LeRoith D. Insulin resistance as the underlying cause for the metabolic syndrome. Med Clin N Am 2007; 91: 1063–1077.

5. Erkkila A, de Mello VDF, Risérus U, Laaksonen DE. Dietary fatty acids and cardiovascular disease: an epidemiological approach. Prog Lipid Res 2008; 47: 172–187.

6. Murff HJ, Edwards TL. Endogenous production of long-chain polyunsaturated fatty acids and metabolic disease risk. Curr Cardiovasc Risk Rep 2014; 8: 418.

7. Glaser C, Heinrich J, Koletzko B. Role of FADS1 and FADS2 polymorphisms in polyunsaturated fatty acid metabolism. Metabolism 2010; 59: 993–999.

8. Lattka E, Illig T, Koletzko B et al. Genetic variants of the FADS1 FADS2 gene cluster as related to essential fatty acid metabolism. Curr Opin Lipidol 2010; 21: 64–69.

9. Merino DM, Johnston H, Clarke S et al. Polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults. Mol Genet Metab 2011; 103: 171–178.

10. Martinelli N, Girelli D, Malerba G et al. 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.

11. Arbo I, Halle C, Malik D et al. Insulin induces fatty acid desaturase expression in human monocytes. Scand J Clin Lab Invest 2011; 71: 330–339.

12. Tosi F, Sartori F, Gustini P et al. Delta-5 and delta-6 desaturase: crucial enzymes in polyunsaturated fatty acid-related pathways with pleitropic influences in health and disease. Adv Exp Med Biol 2014; 114: 1269–1279.

13. Jump DB. N-3 polyunsaturated fatty acid regulation of hepatic gene transcription. Curr Opin Lipidol 2008; 19: 242–247.

14. Hashimoto K, Yoshizawa AC, Saito K et al. The repertoire of desaturases for unsaturated fatty acid synthesis in 397 genomes. Genome Inform 2006; 17: 173–183.

15. Jakobsson A, Westernberg R, Jakobsson A. Fatty acid elongases: their regulation and roles in metabolism. Prog Lipid Res 2006; 45: 237–249.

16. Nakamura MT, Nara TY. Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu Rev Nutr 2004; 24: 345–376.

17. Blanchard H, Legrand P, Pédrono F. Fatty acid desaturase 3 (Fads3) is a singular member of Fadscluster. Biochimie 2011; 93: 87–90.

18. Russo C, Olivieri O, Girelli D. Increased membrane ratios of metabolite to precursor fatty acid in essential hypertension. Hypertension 1997; 29: 1058–1063.

19. Vessby B, Gustafsson IB, Tengblad S et al. Desaturation and elongation of Fatty acids and insulin action. Ann N Y Acad Sci 2002; 967: 183–195.

20. Warensjö E, Öhrvall M, Vessby B. Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women. Nutr Metab Cardiovasc Dis 2006; 16: 128–136.

21. Kröger J, Zietemann V, Enzenbach C et al. Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC) – Potsdam Study. Am J Clin Nutr 2011; 93: 127–142.

22. Kröger J, Schulze MB. Recent insight into the relation of D5 desaturase and D6 desaturase aktivity to the development of type 2 diabetes. Curr Opin Lipidol 2012; 23: 4–10.

23. Žák A, Burda M, Vecka M et al. Fatty acid composition indicates two types of metabolic syndrome independent of clinical and laboratory parameters. Physiol Res 2014; 63 (Suppl. 3): S375–S385.

24. Saito E, Okada T, Abe Y et al. Abdominal adiposity is associated with fatty acid desaturase activity in boys: implications for C-reactive protein and insulin resistance. Prostaglandins Leukot Essent Fatty Acids 2013; 88: 307–311.

25. Armutcu F, Akyol S, Ucar F et al. Markers in nonalcoholic steatohepatitis. Adv Clin Chem 2013; 61: 67–125.

26. Jacobs S, Schiller K, Jansen E et al. Association between erytrocyte membrane fatty acids and biomarkers of dyslipidemia in the EPIC – Potsdam Europ J Clin Nutr 2014; 68: 517–525.

27. Njoroge SW, Seegmiller AC, Katrangi W et al. Increased D5- and D5-6 desaturase, cyclooxygenase-2, and lipoxygenase-5 expression and activity associated with fatty acid and eicosanoid changes in cystic fibrosis. Biochim Biophys Acta 2011; 1811: 431–440.

28. Macášek J, Vecka M, Žák A. et al. Plasma fatty acid composition in patients with pancreatic cancer: correlations to clinical parameters. Nutr Cancer 2012; 64: 946–955.

29. He C, Qu X, Wan J et al. Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. PLoS One 2012; 7: e47567.

30. Pender-Cudlip MC, Krag KJ, Martini D et al. Delta 6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue. Cancer Sci 2013; 104: 760–764.

31. Vařeka T, Vecka M, Jirák R et al. Plasma fatty acid profile in depressive disorder resembles insulin resistance state. Neuroendocrinol Lett 2012; 33(Suppl. 2): 83–86.

32. Liu Y, Jandacek R, Rider T et al. Elevated delta-6 desaturase (FADS2) expression in the postmortem prefrontal cortex of schizophrenic patients: relationship with fatty acid composition. Schizophr Res 2009; 109: 113–120.

33. Liu Y, McNamara RK. Elevated delta-6 desaturase (FADS2) gene expression in the prefrontal cortex of patients with bipolar disorders. J Psychiatr Res 2011; 45: 269–272.

34. Calon F, Limbo, Yang F et al. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer’s disease mouse model. Neuron 2004; 43: 633–645.

35. Schaeffer L, Gohlke H, Müller M et al. 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.

36. Malerba G, Schaeffer L, Xumerle L et al. SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease. Lipids 2008; 43: 289–299.

37. Zietemann V, Kröger J, Enzenbac C et al. Genetic variation of the FADS1 FADS2 gene cluster and n-6 PUFA composition in erythrocyte membranes in the European Prospective Investigation into Cancer and Nutrition – Potsdam. Br J Nutr 2010; 104: 1748–1759.

38. Kwak JH, Paik JK, Kim OY et al. FADS gene polymorphisms in Koreans: association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease. Atherosclerosis 2011; 214: 94–100.

39. Sergeant S, Hugenschmidt CE, Rudock ME et al. Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome. Br J Nutr 2012; 107: 547–555.

40. Mathias RA, Vergara C, Gao L et al. FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population. J Lipid Res 2010; 51: 2766–2774.

41. Bokor S, Dumont J, Spinneker A et al. Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios. J Lipid Res 2010; 51: 2325–2333.

42. Nakayama K, Bayasgalan T, Tazoe F et al. A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle. Hum Genet 2010; 127: 685–690.

43. Tanaka T, Shen J, Abecasis GR et al. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet 2009; 5: e1000338.

44. Stančáková A, Paananen J, Soininen P et al. Effects of 34 risk loci for type 2 diabetes or hyperglycemia on lipoprotein subclasses and their composition in 6,580 nondiabetic Finish men. Diabetes 2011; 60: 1608–1616.

45. Kathiresan S, Willer CJ, Peloso GM et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 2009; 41: 56–65.

46. Dumont J, Huybrechts I, Spinneker A et al. FADS1 genetic variability interacts with dietary α-linolenic acid intake to affect serum non-HDL-cholesterol concentrations in European adolescents. J Nutr 2011; 141: 1247–1253.

47. Sones Y, Kido T, Ainuki T et al. Genetic variants of the fatty acid desaturase gene cluster areassociated with plasma LDL cholesterol in Japanese males. J Nutr Sci Vitaminol 2013; 59: 325–335.

48. Solakivi T, Kunnas O, Jaaakkola O et al. Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro. Lipids Health Dis 2013; 12: 80.

49. Truong H, DiBello JR, Ruiz-Narvaez E et al. Does genetic variation in the D6-desaturase promoter modify the association between α-linolenic acid and the prevalence of metabolic syndrome? Am J Nutr 2009; 89: 920–925.

50. Liu F, Li Z, Lv X, Ma J. Dietary polyunsaturated fatty acid intake modifies the effect of genetic variation in fatty acid desaturase 12 on coronary artery disease. Plos One 2015; 10: e0121255.

51. Lu Y, Feskens EJ, Dollé ME et al. Dietary n-3 and n-6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the Doetinchem Cohort Study. Am J Clin Nutr 2010; 92: 258–265.

52. Hellstrand S, Sonestedt E, Ericson U et al. Intake levels of dietary long-chain PUFAs modify the association between genetic variation in FADS and LDL-C. J Lipid Res 2012; 53: 1183–1189.

53. Cormier H, Rudkowska I, Paradis AM et al. 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.

54. Cormier H, Rudkowska I, Thifault E et al. Polymorphism in fatty acid desaturase (FADS) gene cluster: effects on glycemic controls following an omega-3 polyunsaturated fatty acids (PUFA) supplementation. Genes 2013; 4: 485–498.

55. Ebbesson SOE, Lopez-Alvarenga JC, Okin PM et al. Heart rate is associated with markers of fatty acid desaturation: the GOCADAN study. Int J Circumpolar Healt 2012; 71: 17343.

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