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Fatty acid elongases and their involvement in the pathogenesis of disease states


Authors: M. Zeman;  J. Macášek;  M. Vecka;  B. Staňková;  A. Žák
Authors place of work: IV. Interní klinika, 1. LF UK a VFN v Praze, U Nemocnice 2, Praha 2, 128 01
Published in the journal: Klin. Biochem. Metab., 27, 2019, No. 2, p. 66-71

Summary

Fatty acids possess plenty of functions in human organism. They take a part in regulation of the structure and function of cell membranes and signal pathways, transcription factors activities and gene expression. Fatty acid profiles in the individual tissues are determined by dietary intake, endogenous synthesis, catabolism and as well by desaturation and elongation processes, that are catalysed by the enzymes – desaturases and elongases. Elongases play a principal role in the synthesis of very long chain fatty acids (chain with 22 or more carbons), both saturated and unsaturated. Dysregulation of fatty acid metabolism was recognized to be associated with many diseases, such as atherosclerosis and its complications, type 2 diabetes mellitus, neuropsychiatric and malignant diseases, as well. Activities of fatty acid elongases could serve as significant markers of abovementioned diseases. Moreover, modulation of elongase activities could represent a therapeutic option in some cases.

Keywords:

Metabolism – fatty acids – desaturases – elongases


Zdroje

1. Calder, P. C. Functional Roles of Fatty Acids and Their Effects on Human Health. J. Parenter. Enteral. Nutr., 2015, 39, Suppl 1, p.18-32.

2. 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(5), p.348-80.

3. Sampath, H., Ntambi, J. M. Stearoyl-coenzyme A desaturase 1, sterol regulatory element binding protein-1c and peroxisome proliferator-activated receptor-alpha: independent and interactive roles in the regulation of lipid metabolism. Curr. Opin. Clin. Nutr. Metab. Care., 2006, 9(2), p. 84-8.

4. Meesapyodsuk, D., Qiu, X. The front-end desaturase: structure, function, evolution and biotechnological use. Lipids, 2012, 47, p.227–237.

5. Simopoulos, A. P. Essential fatty acids in health and chronic disease. Am. J Clin. Nutr., 1999, 70, Suppl 3, p. 560-569.

6. Žák, A., Slabý, A., Tvrzická, E., Jáchymová, M., Macášek, J., Vecka, M., et al. Desaturases of fatty acids (FADS) and their physiological and clinical implication. Cas. Lek. Cesk., 2016,155(2), p.15-21.

7. Guillou, H., Zadravec, D., Martin, P. G., Jacobsson, A. The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice. Prog. Lipid Res., 2010, 49, p.186–199.

8. Denic, V., Weissman, J. S. A molecular caliper me-
chanism for determining very long-chain fatty acid length. Cell, 2007, 130, p. 663-677.

9. Mandal, M. N., Ambasudhan, R., Wong, P. W., Gage, P. J., Sieving, P. A., Ayyagari, R. Characterization of mouse orthologue of ELOVL4: genomic organization and spatial and temporal expression. Genomics, 2004, 83, p. 626-635.

10. Tvrdik, P., Westerberg, R., Silve, S., Asadi, A., Jakobsson, A., Cannon, B., Loison, G., Jacobsson, A. Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids. J Cell Biol. 2000 May 1;149(3):707-18.

11. Suneja, S. K., Nagi, M. N., Cook, L., and Cinti, D. L. 1991. Decreased long-chain fatty acyl CoA elongation activity in quaking and jimpy mouse brain: deficiency in one enzyme or multiple enzyme activities? J. Neurochem. 57:140–146.

12. Pauter, A. M., Olsson, P., Asadi, A., Herslöf, B., Csikasz, R. I., Zadravec, D., Jacobsson, A. Elovl2 ablation demonstrates that systemic DHA is endogenously produced and is essential for lipid homeostasis in mice. J. Lipid Res., 2014,55, p. 718–728.

13. de la Garza Puentes, A., Montes Goyanes, R., Chisaguano Tonato, A. M., Torres-Espínola, F. J., Arias García, M., de Almeida, L. et al. Association of maternal weight with FADS and ELOVL genetic variants and fatty acid levels - The PREOBE follow-up. PLoS One., 2017, 9,12(6):e0179135.

14. Tanaka, T., Shen, J., Abecasis, G. R., Kisialiou, A., Ordovas, J. M., Guralnik, J. M., Singleton, A., Bandinelli, S., Cherubini, A., Arnett, D. et al. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet., 2009, 5 :e1000338 .

15. Sun, C., Zou, M., Wang, X., Xia, W., Ma, Y., Liang, S., et al. FADS1-FADS2 and ELOVL2 gene polymorphisms in susceptibility to autism spectrum disorders in Chinese children. BMC Psychiatry., 2018, 4,18(1), 283.

16. Westerberg, R., Månsson, J. E., Golozoubova, V., et al. Elovl3 Is an important component for early onset of lipid recruitment in brown adipose tissue. J Biol. Chem., 2006, 281(8), p. 4958–4968.

17. Ohno, Y., Suto, S., Yamanaka, M., Mizutani, Y., Mitsutake, S., Igarashi, Y., Sassa, T., Kihara, A. ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis, Proc. Natl. Acad. Sci. U. S. A., 2010, p. 1–6.

18. Agbaga, M. P., Mandal, M. N., Anderson, R. E. Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein. J. Lipid Res., 2010, 51, p. 1624-1642.

19. Karan, G., Lillo, C., Yang, Z., Cameron, D. J., Locke, K. G., Zhao, Y., et al. Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration. Proc Natl Acad Sci U S A., 2005, 15, 102(11), p. 4164-9.

20. Wang, Y., Botolin, D., Xu, J., et al. Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesity. Journal of lipid research., 2006, 47(9), p. 2028-2041.

21. Tripathy, S., Jump, D.B. Elovl5 regulates the mTORC2-Akt-FOXO1 pathway by controlling hepatic cis-vaccenic acid synthesis in diet-induced obese mice. J Lipid Res., 2013, 54(1), p. 71-84.

22. Tripathy, S., Torres-Gonzalez, M., Jump, D. B. Elevated hepatic fatty acid elongase-5 activity corrects dietary fat-induced hyperglycemia in obese C57BL/6J mice. J. Lipid Res., 2010, 51, p. 2642–2654.

23. Li, X., Gan, Z. W., Ding, Z., et al. Genetic Variants in the ELOVL5 but not ELOVL2 Gene Associated with Polyunsaturated Fatty Acids in Han Chinese Breast Milk. Biomed. Environ. Sci., 2017, 30(1), p. 64-67.

24. Di Gregorio, E., Borroni, B., Giorgio, E., Lacerenza, D., Ferrero, M., Lo Buono, N., et al. ELOVL5 mutations cause spinocerebellar ataxia 38. Am J Hum. Ge-net., 2014, 7, 95(2), p. 209-17.

25. Petty, H. R. Frontiers of Complex Disease Mechanisms: Membrane Surface Tension May Link Genotype to Phenotype in Glaucoma Front. Cell Dev. Biol., 2018, 06, https://doi.org/10.3389/fcell.2018.00032.

26. Aslibekyan, S., Jensen, M. K., Campos, H., Linkletter, C. D., Loucks, E. B., Ordovas, J. M., et al. Genetic variation in fatty acid elongases is not associated with intermediate cardiovascular phenotypes or myocardial infarction. Eur J Clin. Nutr., 2012, 66(3), p. 353-9.

27. Matsuzaka, T., Shimano, H., Yahagi, N., Kato, T., Atsumi, A., Yamamoto, T. et al. Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nat. Med., 2007, 13(10), p. 1193-202.

28. Tang, N., Matsuzaka, T., Suzuki, M., Nakano, Y., Zao, H., Yokoo, T., et al. Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion. Biochem. Biophys. Res. Commun., 2014, 18 450(1), p. 318-23.

29. Zhao, H., Matsuzaka, T., Nakano, Y., Motomura, K., Tang, N., Yokoo, T. et al. Elovl6 Deficiency Improves Glycemic Control in Diabetic db/db Mice by Expanding β-Cell Mass and Increasing Insulin Secretory Capacity. Diabetes, 2017, 66(7), p. 1833-1846.

30. Su, Y. C., Feng, Y. H., Wu, H. T., Huang, Y. S., Tung, C. L., Wu, P. et al. Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression. Sci Rep., 2018, 26, 8(1), p. 6586.

31. Pickens, C. A., Lane-Elliot, A., Comstock, S. S., Fenton, J. I. Altered Saturated and Monounsaturated Plasma Phospholipid Fatty Acid Profiles in Adult Males with Colon Adenomas. Cancer Epidemiol. Biomarkers Prev., 2016, 25(3), p. 498-506.

32. Morcillo, S., Martín-Núnez, G. M., Rojo-Martínez, G., Almaraz, M. C., García-Escobar, E. et al. ELOVL6 Genetic Variation Is Related to Insulin Sensitivity: A New Candidate Gene in Energy Metabolism. PLoS ONE., 2011, 6(6), e21198.

33. Liu, Y., Wang, F., Yu, X. L., Miao, Z. M., Wang, Z. C., Chen, Y., Wang, Y. Genetic analysis of the ELOVL6 gene polymorphism associated with type 2 diabetes mellitus. Brazilian Journal of Medical and Biological Research., 2013, 46, p. 623-628.

34. Tamura, K., Makino, A., Hullin-Matsuda, F., Kobayashi, T., Furihata, M., Chung, S., et al. Novel lipogenic enzyme ELOVL7 is involved in prostate cancer growth through saturated long-chain fatty acid metabolism. Cancer Res., 2009, 69, p. 8133-8140.

Štítky
Clinical biochemistry Nuclear medicine Nutritive therapist

Článok vyšiel v časopise

Clinical Biochemistry and Metabolism

Číslo 2

2019 Číslo 2

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