Effects of Nutrient-Gene Interactions on Metabolic Diseases

Abstract

Metabolic diseases are major global health problems caused by genetic predisposition and nutritional factors. Advances in nutrigenomics have enabled the development of nutritional strategies by revealing the effects of nutrients on gene expression. This review mentions different investigations related to the role of nutrient-gene interactions in metabolic diseases including obesity, diabetes, cancer, and non-alcoholic fatty liver disease. The findings showed that secondary metabolites, macronutrients, and micronutrients can influence diseases by regulating gene expressions. Understanding the complex interactions between nutrients and genes will contribute to developing disease prevention and treatment strategies with fewer or no side effects.

Keywords

• cancer
• diabetes
• nutrigenomics
• nutrigenetics
• non-alcoholic fatty liver disease
• obesity

References

1. Cheng, Z., Zheng, L.and F. A. Almeida, Epigenetic reprogramming in metabolic disorders: nutritional factors and beyond. The Journal of Nutritional Biochemistry, 2018. 54: 1–10. Doi: 10.1016/j.jnutbio.2017.10.004.
2. Yang, M., Liu, S. and C. Zhang, The related metabolic diseases and treatments of obesity. Healthcare,2022. 10(9): 1616. Doi: 10.3390/healthcare10091616.
3. A. C. Frazier-Wood, Dietary patterns, genes, and health: challenges and obstacles to be overcome. Curr Nutr Rep, 2015. 4(1):82–87. Doi: 10.1007/s13668-014-0110-6.
4. Birla, M. et al., The Advent of nutrigenomics: A Narrative Review with an Emphasis on Psychological Disorders. Prev Nutr Food Sci, 2022. 27(2): 150–164. Doi: 10.3746/pnf.2022.27.2.150.
5. Kiani, A. K.et al., Polymorphisms, diet and nutrigenomics. Journal of Preventive Medicine and Hygiene, 2022. 63(2): E125. Doi: 10.15167/2421-4248/jpmh2022.63.2S3.2754.
6. Marcum, J. A., Nutrigenetics/Nutrigenomics, Personalized Nutrition, and Precision Healthcare. Curr Nutr Rep, 2020. 9(4):338–345. Doi: 10.1007/s13668-020-00327-z.
7. Mondal, S. and Panda, D., Nutrigenomics: An Interface of Gene-Diet-Disease Interaction. Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface, IntechOpen, 2020. Doi: 10.5772/intechopen.94602.
8. Beck, A. P. and Meyerholz, D. K., Evolving challenges to model human diseases for translational research. Cell Tissue Res, 2020. 380(2): 305–311. Doi: 10.1007/s00441-019-03134-3.

9. Daneshian M. et al., Animal use for science in Europe. Alternatives to Animal Experimentation, 2015. 32(4):261–274. Doi: 10.14573/altex.1509081.
10. Wang, H. et al., Genome-scale metabolic network reconstruction of model animals as a platform for translational research. Proceedings of the National Academy of Sciences, 2021. 118(30): e2102344118. Doi: 10.1073/pnas.2102344118.
11. Weng G.et al., Plant Extracts in Obesity: A Role of Gut Microbiota. Frontiers in Nutrition, 2021. 8:727951. Doi: 10.3389/fnut.2021.727951.
12. Lin, X. and H. Li, Obesity: Epidemiology, Pathophysiology, and Therapeutics. Front Endocrinol (Lausanne), 2021. 12:706978. Doi: 10.3389/fendo.2021.706978.
13. Sankararaman, S. et al., Gut Microbiome and Its Impact on Obesity and Obesity-Related Disorders. Curr Gastroenterol Rep, 2023. 25(29):31–44. Doi: 10.1007/s11894-022-00859-0.
14. Safaei, M. et al., A systematic literature review on obesity: Understanding the causes & consequences of obesity and reviewing various machine learning approaches used to predict obesity. Computers in Biology and Medicine 2021. 136:104754. Doi: 10.1016/j.compbiomed.2021.104754.
15. Akram D. S.et al.Obesity: Preventing and managing the global epidemic. World Health Organization Technical Report Series, 2000. 894:i-xii, 1-253. PMID: 11234459 229
16. Fruh S. M., Obesity: Risk factors, complications, and strategies for sustainable long‐term weight management. J Am Assoc Nurse Pract, 2017. 29(1):3–14. Doi: 10.1002/2327-6924.12510.
17. Pelczyńska, M. et al., The Preventive Mechanisms of Bioactive Food Compounds against Obesity-Induced Inflammation. Antioxidants, 2023. 12(6) Doi: 10.3390/antiox12061232.
18. Kushner, R. F., Medical management of obesity. Semin Gastrointest Dis., 2002. 13(3):123–132. PMID: 12230315
19. Askari, A. et al., The surgical management of obesity. Clinical Medicine, 2023. 23(4):330. Doi: 10.7861/clinmed.2023 0189.
20. Onakpoya, I. J., C. J. Heneghan, and J. K. Aronson, Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. BMC Medicine, 2016. 14(1):191. Doi: 10.1186/s12916-016-0735-y.
21. Shama, A. T. et al., Anti-obesity effects and underlying molecular mechanisms of the ethanolic extract of figs from Ficus hispida using high fat-fed wister rats. Heliyon, 2024. 10(15):e35392. Doi: 10.1016/j.heliyon.2024.e35392.
22. Lee, Y.S.et al., The ethanolic extract of Korean Curcuma longa rhizome inhibits adipogenesis in 3T3-L1 adipocytes and high-fat diet-induced obese mice via activating AMPK signaling pathway. Journal of Functional Foods, 2023. 110:105854. Doi: 10.1016/j.jff.2023.105854.
23. Elebishehy, A.et al., ‘Cymbopogon schoenanthus (L) extract ameliorates high fat diet-induced obesity and dyslipidemia via reducing expression of lipogenic and thermogenic proteins. Fitoterapia, 2024. 175:105897. Doi: 10.1016/j.fitote.2024.105897.
24. Yang T. et al., An update on chronic complications of diabetes mellitus: from molecular mechanisms to therapeutic strategies with a focus on metabolic memory. Molecular Medicine, 2024. 30(1)71. Doi: 10.1186/s10020-024-00824-9.
25. Sun, H.et al., IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract, 2022. 183:109119. Doi: 10.1016/j.diabres.2021.109119. American Diabetes Association, Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 2013. 37(1):81–90. Doi: 10.2337/dc14-S081.
26. Guzman-Vilca, W. C. and R. M. Carrillo-Larco, Number of People with Type 2 Diabetes Mellitus in 2035 and 2050: A Modelling Study in 188 Countries. Curr Diabetes Rev, 2024. 21(1)e120124225603. Doi: 10.2174/0115733998274323231230131843.
27. Agunloye, M. O., et al., The role of avocado plant and its derivatives in the management of diabetes mellitus: a natural approach to glycemic control. J Diabetes Metab Disord, 2025. 24(1): 34. Doi: 10.1007/s40200-024-01551-y.
28. Widowati, W. et al., Butterfly pea flower (Clitoria ternatea L.) extract displayed antidiabetic effect through antioxidant, anti-inflammatory, lower hepatic GSK-3β, and pancreatic glycogen on Diabetes Mellitus and dyslipidemia rat. Journal of King Saud University - Science, 2023. 35(4): p. 102579, Doi: 10.1016/j.jksus.2023.102579.
29. Shen, L. et al., Buckwheat extracts rich in flavonoid aglycones and flavonoid glycosides significantly reduced blood glucose in diabetes mice. Journal of Functional Foods, 2024. 113:106029. Doi: 10.1016/j.jff.2024.106029.
30. Yang X. et al., Corni Fructus extracts ameliorate Streptozotocin-Induced diabetes in mice via regulating AMPK/ACC/CPT 1 signaling pathway. Journal of Functional Foods, 2023. 107:105661. Doi: 10.1016/j.jff.2023.105661.
31. Sung, H. et al., Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 2021. 71(3):209–249. Doi: 10.3322/caac.21660.
32. Bray, F. et al., Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 2024. 74(3):229–263. Doi: 10.3322/caac.21834.
33. Sudhakar, A., History of Cancer, Ancient and Modern Treatment Methods. J Cancer Sci Ther, 2009. 1(2): 1–4. Doi: 0.4172/1948-5956.100000e2.
34. Malcomson, F. C. and Mathers, J. C., Translation of nutrigenomic research for personalised and precision nutrition for cancer prevention and for cancer survivors. Redox Biology, 2023. 62:102710. Doi: 10.1016/j.redox.2023.102710.
35. Hao, X., et al., Green Tea Polyphenols Inhibit Colorectal Tumorigenesis in Azoxymethane-Treated F344 Rats’, Nutr Cancer, 2017. 69(4):623–631. Doi: 10.1080/01635581.2017.1295088.
36. Ragni, M., et al., An amino acid-defined diet impairs tumour growth in mice by promoting endoplasmic reticulum stress and mTOR inhibition. Molecular Metabolism, 2022. 60:101478. Doi: 10.1016/j.molmet.2022.101478.
37. Li, S., et al., Paternal Combined Botanicals Contribute to the Prevention of Estrogen Receptor–Negative Mammary Cancer in Transgenic Mice. The Journal of Nutrition, 2023. 153(7):1959–1973. Doi: 10.1016/j.tjnut.2023.05.001.
38. Brane, A., I. Arora, and T. O. Tollefsbol, Peripubertal Nutritional Prevention of Cancer-Associated Gene Expression and Phenotypes. Cancers (Basel), 2023. 15(3):674. Doi: 10.3390/cancers15030674.
39. Parra, M., S. Stahl, and H. Hellmann, Vitamin B6 and Its Role in Cell Metabolism and Physiology. Cells, 2018. 7(7):84. Doi: 10.3390/cells7070084.
40. Pilesi, E.et al., A gene-nutrient interaction between vitamin B6 and serine hydroxymethyltransferase (SHMT) affects genome integrity in Drosophila. Journal of Cellular Physiology, 2023. 238(7):1558–1566. Doi: 10.1002/jcp.31033.
41. Ferramosca, A., M. D. Giacomo, and V. Zara, Antioxidant dietary approach in treatment of fatty liver: New insights and updates. World Journal of Gastroenterology, 2017. 23(23):4146. Doi: 10.3748/wjg.v23.i23.4146.
42. Zaiou, M., et al., Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease. Biomedicines, 2021. 9(9):1256. Doi: 10.3390/biomedicines9091256.
43. Hosseini, H. et al., Resveratrol alleviates non-alcoholic fatty liver disease through epigenetic modification of the Nrf2 signaling pathway. Int J Biochem Cell Biol, 2020. 119:105667. Doi: 10.1016/j.biocel.2019.105667.
44. Wang, Q. et al., Total flavonoids of Broussonetia papyrifera alleviate non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signaling pathways. Biochim Biophys Acta Mol Cell Biol Lipids, 2024. 1869(5):159497. Doi: 10.1016/j.bbalip.2024.159497. Assa-Glazer, T., et al., Cannabis Extracts Affected Metabolic Syndrome Parameters in Mice Fed High-Fat/Cholesterol Diet. Cannabis Cannabinoid Res, 2020. 5(3): 202–214. Doi: 10.1089/can.2020.0013.
45. Chang, Y.C. et al., Mulberry leaf extract inhibits obesity and protects against diethylnitrosamine-induced hepatocellular carcinoma in rats. Journal of Traditional and Complementary Medicine, 2024. 14(3):266–275. Doi: 10.1016/j.jtcme.2024.01.007.
46. Jako, P. et al., Passiflora edulis extract ameliorates HFD-induced hepatic steatosis mediated through Nrf2 and IRS-1 activation, NFκB suppression, and hepatic lipid metabolism and bile acid modulation in obese rats. Journal of Functional Foods, 2024. 120:106351. Doi: 10.1016/j.jff.2024.106351.