Beslenmede Metilasyon Döngüsü Kavramı ve Hastalık İlişkileri

Etkisi en çok araştırılmış epigenetik mekanizma olan metilasyon; genomun normal yapıda düzenlenmesini sağlayan kimyasal bir tepkimedir. DNA metilasyon kalıpları, gelişim ve yaşlanma ile birlikte değişir, hücre tipleri arasında farklılık gösterir. Metilasyondaki bozukluklar birçok hastalığın patogenezinde rol oynar. Epigenetik süreçte beslenmenin rolü büyüktür. DNA metilasyon kalıpları diyet faktörleri tarafından modüle edilebilir. Kötü beslenme alışkanlıkları metabolik ya da kimyasal modifikasyonlara neden olarak gen ekspresyonu değiştirebilir. Özellikle kanser, obezite, kardiyovasküler hastalıklar, diyabet gibi hastalıklardaki metilasyon döngüsünün rolünün bilinmesi bu hastalıkların patogenezinin aydınlatılması için büyük önem arz etmektedir. Bu derlemede metilasyon döngüsü, beslenmede metilasyon döngüsü kavramı ve hastalık ilişkileri anlatılmıştır.

Anahtar Kelimeler:

DNA Metilasyonu, Epigenetik, Beslenme, DNA Methylation, Epigenetics, Nutrition.

The Concept of Methylation Cycle in Nutrition and Its Relationships

Methylation, which is the most studied epigenetic mechanism, is a chemical reaction that allows the genome to be arranged in its normal structure. DNA methylation patterns change with development and aging, differing between cell types. Disorders in methylation play a role in the pathogenesis of many diseases. Nutrition plays an important role in the epigenetic process. DNA methylation patterns can be modulated by dietary factors. Poor dietary habits can alter gene expression by causing metabolic or chemical modifications. Understanding the role of the methylation cycle in diseases such as cancer, obesity, cardiovascular diseases, diabetes is of considerable importance for elucidating the pathogenesis of diseases. In this review, the methylation cycle, the concept of the methylation cycle in nutrition and disease relationships are explained.

Keywords:

DNA Methylation, Epigenetics, Nutrition,

PDF

___

1. Pizzorusso, T., & Tognini, P. (2020). Interplay between Metabolism, Nutrition and Epigenetics in Shaping Brain DNA Methylation, Neural Function and Behavior. Genes, 11(7), 742.
2. Zhang, N. (2015). Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals. Anim Nutr, 1(3), 144-151.
3. Anderson, O. S., Sant, K. E., & Dolinoy, D. C. (2012). Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem, 23(8), 853–859.
4. Merdol, T. K. (2018). DNA metilasyonu ve beslenme. Bes Diy Der, 46(2), 103-106.
5. Glier, M. B., Green, T. J., & Devlin, A. M. (2014). Methyl nutrients, DNA methylation, and cardiovascular disease. Mol Nutr Food Res, 58(1), 172-182.
6. Güler, C., & Balcı Peynircioğlu, B. (2016). DNA metilasyonu ve hastalıklarla ilişkisi. Acıbadem Univ Sağlık Bilim Derg, (2):61-68.
7. ElGendy, K., Malcomson, F. C., Lara, J. G., Bradburn, D. M., & Mathers, J. C. (2018). Effects of dietary interventions on DNA methylation in adult humans: systematic review and meta-analysis. Br J Nutr, 120(9), 961– 976.
8. Kadayifci, F. Z., Zheng, S., & Pan, Y. X. (2018). Molecular mechanisms underlying the link between diet and DNA methylation. Int J Mol Sci, 19(12), 4055.
9. Koban, B. U., Vural, E. Z. T., Işıtmangil, G., & Gönenç, I. (2017). Beslenme, diğer çevresel faktörler ve mikrobiyotanın obezite epigenetiğine etkileri. TJTFP, 8(4), 108-117.
10. Parrillo, L., Spinelli, R., Nicolò, A., Longo, M., Mirra, P., Raciti, G. A. et al. (2019). Nutritional factors, DNA methylation, and risk of type 2 diabetes and obesity: Perspectives and challenges. Int J Mol Sci, 20(12), 2983.
11. Crider, K. S., Quinlivan, E. P., Berry, R. J., Hao, L., Li, Z., Maneval, D. et al. (2011). Genomic DNA methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age. PloS One, 6(12), e28144.
12. Vukic, M., & Daxinger, L. (2019). DNA methylation in disease: Immunodeficiency, Centromeric instability, Facial anomalies syndrome. Essays biochem, 63(6), 773–783.
13. Ayaz, G. B., Şahin, Ö., Ayaz, U., & Özdemir, S. M. (2019). Epigenetik ve kanser. Madde, Diyalektik ve Toplum, 2(1), 94-103.
14. Ehrlich M. (2019). DNA hypermethylation in disease: mechanisms and clinical relevance. Epigenetics, 14(12), 1141–1163.
15. Jones, P. A., & Buckley, J. D. (1990). The role of DNA methylation in cancer. Adv Cancer Res, 54, 1-23.
16. Blom, H. J. (2009). Folic acid, methylation and neural tube closure in humans. Birth Defects Res A Clin Mol Teratol, 85(4), 295-302.
17. Rochtus, A., Jansen, K., Geet, C. V., & Freson, K. (2015). Nutri-epigenomic studies related to neural tube defects: does folate affect neural tube closure via changes in DNA methylation?. Mini Rev Med Chem, 15(13), 1095-1102.
18. Chang, H., Zhang, T., Zhang, Z., Bao, R., Fu, C., Wang, Z. et al. (2011). Tissue-specific distribution of aberrant DNA methylation associated with maternal low-folate status in human neural tube defects. J Nutr Biochem, 22(12), 1172-1177.
19. Szabo, L., Molnar, R., Tomesz, A., Deutsch, A., Darago, R., Nowrasteh, G. et al. (2021). The effects of flavonoids, green tea polyphenols and coffee on DMBA induced LINE-1 DNA hypomethylation. PLoS One, 16(4), e0250157.
20. Lim, U., & Song, M. A. (2012). Dietary and lifestyle factors of DNA methylation. Methods Mol Biol, 863, 359–376.
21. Li, Y., & Tollefsbol, T. O. (2010). Impact on DNA methylation in cancer prevention and therapy by bioactive dietary components. Curr Med Chem, 17(20), 2141–2151.
22. Arpón, A., Milagro, F. I., Razquin, C., Corella, D., Estruch, R., Fitó, M. et al. (2017). Impact of consuming extra-virgin olive oil or nuts within a Mediterranean diet on DNA methylation in peripheral white blood cells within the PREDIMED-Navarra randomized controlled trial: A role for dietary lipids. Nutrients, 10(1), 15.
23. Gil-Zamorano, J., Martin, R., Daimiel, L., Richardson, K., Giordano, E., Nicod, N. et al. (2014). Docosahexaenoic acid modulates the enterocyte Caco-2 cell expression of microRNAs involved in lipid metabolism. J Nutr, 144(5), 575–585.
24. Boqué, N., de la Iglesia, R., de la Garza, A. L., Milagro, F. I., Olivares, M., Bañuelos, O., et al. (2013). Prevention of diet-induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns. Mol Nutr Food Res, 57(8), 1473–1478.
25. Ramos-Lopez, O., Milagro, F. I., Allayee, H., Chmurzynska, A., Choi, M. S., Curi, R. et al. (2017). Guide for current nutrigenetic, nutrigenomic, and nutriepigenetic approaches for precision nutrition ınvolving the prevention and management of chronic diseases associated with obesity. J Nutrigenet Nutrigenomics, 10(1-2), 43-62.
26. Gensous, N., Franceschi, C., Santoro, A., Milazzo, M., Garagnani, P., & Bacalini, M. G. (2019). The ımpact of caloric restriction on the epigenetic signatures of aging. Int J Mol Sci, 20(8), 2022.
27. Nicoletti, C. F., Nonino, C. B., de Oliveira, B. A., Pinhel, M. A., Mansego, M. L., Milagro, F. et al. (2016). DNA methylation and hydroxymethylation levels in relation to two weight loss strategies: Energy-restricted diet or bariatric surgery. Obes Surg, 26(3), 603–611.
28. Rees, W. D., Hay, S. M., Brown, D. S., Antipatis, C., & Palmer, R. M. (2000). Maternal protein deficiency causes hypermethylation of DNA in the livers of rat fetuses. J Nutr, 130(7), 1821–1826.
29. Heijmans, B. T., Tobi, E. W., Stein, A. D., Putter, H., Blauw, G. J., Susser, E. S. et al. (2008). Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A, 105(44), 17046–17049.
30. Tobi, E. W., Slagboom, P. E., van Dongen, J., Kremer, D., Stein, A. D., Putter, H. et al. (2012). Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19. PloS One, 7(5), e37933.
31. Wilhelmi de Toledo, F., Grundler, F., Sirtori, C. R., & Ruscica, M. (2020). Unravelling the health effects of fasting: a long road from obesity treatment to healthy life span increase and improved cognition. Ann Med, 52(5), 147–161.
32. Golbidi, S., Daiber, A., Korac, B., Li, H., Essop, M. F., & Laher, I. (2017). Health benefits of fasting and caloric restriction. Curr Diab Rep, 17(12), 123.
33. Mattson, M. P., Longo, V. D., & Harvie, M. (2017). Impact of intermittent fasting on health and disease processes. Ageing Res Rev, 39, 46–58.
34. Campión, J., Milagro, F. I., Goyenechea, E., & Martínez, J. A. (2009). TNF-alpha promoter methylation as a predictive biomarker for weight-loss response. Obesity, 17(6), 1293–1297.
35. Kalea, A. Z., Drosatos, K., & Buxton, J. L. (2018). Nutriepigenetics and cardiovascular disease. Curr Opin Clin Nutr Metab Care, 21(4), 252–259.
36. Sarıgöl, Z. (2014). Epigenetik değişiklikler ve beslenme ilişkisi. Turkiye Klinikleri J Pharm Sci, 3(2):74-80.
37. Fang, M. Z., Chen, D., Sun, Y., Jin, Z., Christman, J. K., & Yang, C. S. (2005). Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res, 11(19 Pt 1), 7033–7041.
38. Mierziak, J., Kostyn, K., Boba, A., Czemplik, M., Kulma, A., & Wojtasik, W. (2021). Influence of the bioactive diet components on the gene expression regulation. Nutrients, 13(11), 3673.
39. van Dijk, S. J., Tellam, R. L., Morrison, J. L., Muhlhausler, B. S., & Molloy, P. L. (2015). Recent developments on the role of epigenetics in obesity and metabolic disease. Clin Epigenetics, 7, 66.
40. Sırıken, B., Sırıken, F., Ünsal, C., & Çiftci, G. (2018). Beslenme ve Epigenetik. Harran Üniv Vet Fak Derg, 7, 12-18.
41. Güneş, S., & Bayramov, B. (2016). Yaşlanma ve yaşlanmayla ilişkili hastalıklardaki epigenetik değişiklikler. Turkiye Klinikleri J Med Sci, 36(3):162-70.
42. Ma, Y., & Ordovas, J. M. (2017). The integration of epigenetics and genetics in nutrition research for CVD risk factors. The Proc Nutr Soc, 76(3), 333–346.
43. Tuttolomondo, A., Simonetta, I., Daidone, M., Mogavero, A., Ortello, A., & Pinto, A. (2019). Metabolic and vascular effect of the Mediterranean diet. Int J Mol Sci, 20(19), 4716.
44. Ling, C., & Rönn, T. (2019). Epigenetics in human obesity and type 2 diabetes. Cell Metab, 29(5), 1028–1044.
45. Sharp, G. C., Lawlor, D. A., Richmond, R. C., Fraser, A., Simpkin, A., Suderman, M. et al. (2015). Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children. Int J Epidemiol, 44(4), 1288–1304.
46. He, F., Berg, A., Imamura Kawasawa, Y., Bixler, E. O., Fernandez-Mendoza, J., Whitsel, E. A., et al. (2019). Association between DNA methylation in obesity-related genes and body mass index percentile in
adolescents. Scientific reports, 9(1), 2079.
47. Milagro, F. I., Campión, J., Cordero, P., Goyenechea, E., Gómez-Uriz, A. M., Abete, I. et al. (2011). A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet-induced weight loss. FASEB J, 25(4), 1378–1389.
48. Nilsson, E., Matte, A., Perfilyev, A., de Mello, V. D., Käkelä, P., Pihlajamäki, J. et al. (2015). Epigenetic alterations in human liver from subjects with type 2 diabetes in parallel with reduced folate levels. J Clin Endocrinol Metab, 100(11), E1491–E1501.
49. Hong, S. M., Woo, H. W., Kim, M. K., Kim, S. Y., Lee, Y. H., Shin. et al. (2017). A prospective association between dietary folate intake and type 2 diabetes risk among Korean adults aged 40 years or older: the Korean Multi-Rural Communities Cohort (MRCohort) Study. Br J Nutr, 118(12), 1078–1088.
50. Gregory, J. F., 3rd, Swendseid, M. E., & Jacob, R. A. (2000). Urinary excretion of folate catabolites responds to changes in folate intake more slowly than plasma folate and homocysteine concentrations and lymphocyte DNA methylation in postmenopausal women. J Nutr, 130(12), 2949–2952.
51. Gama-Sosa, M. A., Slagel, V. A., Trewyn, R. W., Oxenhandler, R., Kuo, K. C., Gehrke, C. et al. (1983). The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Res, 11(19), 6883–6894.
52. Hatipoğlu, Ö. F., Kaya, E., Yaykaşlı, E., & Yaykaşlı, K. O. (2012). Epigenetik mekanizmalar ve kanser. Düzce Tıp Fak Derg, 14(3), 58-68.
53. Sayın, D. B. (2008). Metilasyon ve kanser. Turkiye Klinikleri J Med Sci, 28(4):513-524.
54. Nishiyama, A., & Nakanishi, M. (2021). Navigating the DNA methylation landscape of cancer. Trends Genet, 37(11), 1012–1027.
55. Köhler, F., & Rodríguez-Paredes, M. (2020). DNA Methylation in Epidermal Differentiation, Aging, and Cancer. J Invest Dermatol, 140(1), 38–47.
56. Robertson K. D. (2005). DNA methylation and human disease. Nat Rev Genet, 6(8), 597–610.
57. Sapienza, C., & Issa, J. P. (2016). Diet, Nutrition, and Cancer Epigenetics. Annu Rev Nutr, 36, 665–681.