Altered Kynurenine Pathway Metabolism in Rats Fed Added Sugars

Bahadir Ozturk; Duygu Eryavuz Onmaz

doi:10.54005/geneltip.1140308

Araştırma Makalesi

İlave şekerlerle beslenen ratlarda değişmiş kinürenin yolağı metabolizması

Yıl 2022, Cilt: 32 Sayı: 5, 525 - 529, 29.10.2022

Bahadir Ozturk Duygu Eryavuz Onmaz

https://doi.org/10.54005/geneltip.1140308

Öz

Aim: The consumption of added sugars containing fructose has increased dramatically. Various studies have revealed that added sugar consumption may be involved in the pathogenesis of cardiovascular, metabolic and neurocognitive disorders by triggering subclinical inflammation. The imbalance in the kynurenine pathway metabolites may be associated with inflammation and oxidative stress. The aim of this study is to investigate the effect of HFCS-55, invert sugar and sucrose intervention on the kynurenine pathway metabolite levels (tryptophan, kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, quinolinic acid and kynurenic acid) in Wistar rats.
Material and Methods: Twenty-four Wistar male rats (8-12 weeks old, weighting 300-350 g) were included in the study. After one week of conditioning, the animals were randomly divided into four groups: chow diet and tap water (control, n = 6), chow diet and tap water including 10% HFCS-55 (55% sucrose, 45% glucose), chow diet and tap water including 10% sucrose, chow diet and tap water including 10% invert sugar (33% sucrose, 66% glucose and fructose). At the end of the 3-month experimental period, serum kynurenines levels were measured by tandem mass spectrometry.
Results: Serum kynurenine levels and kynurenine / tryptophan ratio were significantly higher (p<0.05) and serum kynurenic acid levels were significantly lower (p<0.05) in rats fed with HFCS, sucrose and invert sugar compared to the control group.
Conclusion: Our findings suggest that consumption of added sugar may lead to an imbalance in the kynurenine pathway metabolites. The altered kynurenine metabolism may trigger inflammation and oxidative damage, and may predispose to chronic diseases.

Anahtar Kelimeler

Triptofan, Kinürenin, HFCS, sükroz, enflamasyon

Kaynakça

1. Heidari-Beni M, Kelishadi R. The Role of dietary sugars and sweeteners in metabolic disorders and diabetes. In: Mérillon J-M, Ramawat KG, eds. Sweeteners: Pharmacology, Biotechnology, and Applications. Cham: Springer International Publishing 2018:225-243.
2. Johnson RJ, Nakagawa T, Sanchez-Lozada LG, et al. Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes 2013;62(10):3307-3315.
3. Johnson RJ, Sánchez-Lozada LG, Andrews P, Lanaspa MA. Perspective: A historical and scientific perspective of sugar and its relation with obesity and diabetes. Adv Nutr 2017;8(3):412-422.
4. Rippe JM, Angelopoulos TJ. Added sugars and risk factors for obesity, diabetes and heart disease. Int J Obes (Lond) 2016;40 Suppl 1:S22-27.
5. Parker K, Salas M, Nwosu V. High fructose corn syrup: production, uses and public health concerns Biotechnol Mol Biol Rev 2011;5:71-8.
6. Molz P, Molz W, Dallemole D, et al. Invert sugar induces glucose intolerance but does not cause injury to the pancreas nor permanent DNA damage in rats. Anais da Academia Brasileira de Ciências 2020;92.
7. Rippe JM, Angelopoulos TJ. Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding. Nutrients 2016;8(11):697.
8. Pereira SS, Alvarez-Leite JI. Low-Grade Inflammation, Obesity, and Diabetes. Curr Obes Rep 2014;3(4):422-431.
9. Lopez-Candales A, Hernández Burgos PM, Hernandez-Suarez DF, et al. Linking Chronic Inflammation with Cardiovascular Disease: From Normal Aging to the Metabolic Syndrome. J Nat Sci 2017;3(4).
10. Minihane AM, Vinoy S, Russell WR, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr 2015;114(7):999-1012.
11. Della Corte KW, Perrar I, Penczynski KJ, et al. Effect of dietary sugar intake on biomarkers of subclinical inflammation: a systematic review and meta-analysis of intervention studies. Nutrients 2018;10(5).
12. Ruff JS, Hugentobler SA, Suchy AK, et al. Compared to sucrose, previous consumption of fructose and glucose monosaccharides reduces survival and fitness of female mice. The Journal of nutrition 2015;145(3):434-441.
13. Davis I, Liu A. What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics? Expert Rev Neurother 2015;15(7):719-721.
14. Larkin PB, Sathyasaikumar KV, Notarangelo FM, et al. Tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase 1 make separate, tissue-specific contributions to basal and inflammation-induced kynurenine pathway metabolism in mice. Biochim Biophys Acta 2016;1860(11):2345-2354.
15. Sorgdrager FJH, Naudé PJW, Kema IP, et al. Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target. Front Immunol 2019;10(2565).
16. Savitz J. The kynurenine pathway: a finger in every pie. Mol Psychiatry 2020;25(1):131-147.
17. Chen Y, Guillemin GJ. Kynurenine pathway metabolites in humans: disease and healthy States. Int J Tryptophan Res 2009;2:1-19.
18. Song P, Ramprasath T, Wang H, et al. Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases. Cell Mol Life Sci 2017;74(16):2899-2916.
19. Forrest CM, Kennedy A, Stone TW, et al. Kynurenine and neopterin levels in patients with rheumatoid arthritis and osteoporosis during drug treatment. Adv Exp Med Biol 2003;527:287-295.
20. Tong Q, Song J, Yang G, et al. Simultaneous determination of tryptophan, kynurenine, kynurenic acid, xanthurenic acid and 5-hydroxytryptamine in human plasma by LC-MS/MS and its application to acute myocardial infarction monitoring. Biomedical chromatography: BMC 2018;32(4).
21. Lowndes J, Sinnett S, Pardo S, et al. The effect of normally consumed amounts of sucrose or high fructose corn syrup on lipid profiles, body composition and related parameters in overweight/obese subjects. Nutrients 2014;6(3):1128-1144.
22. Hodge AM, English DR, O'Dea K, et al. Glycemic index and dietary fiber and the risk of type 2 diabetes. Diabetes Care 2004;27(11):2701-2706.
23. Sievenpiper JL, de Souza RJ, Mirrahimi A, et al. Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Ann Intern Med 2012;156(4):291-304.
24. Jacobs DR, Jr., Meyer KA, Kushi LH, et al. Whole-grain intake may reduce the risk of ischemic heart disease death in postmenopausal women: the Iowa Women's Health Study. Am J Clin Nutr 1998;68(2):248-257.
25. Aeberli I, Gerber PA, Hochuli M, et al. Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial. Am J Clin Nutr 2011;94(2):479-485.
26. Jin R, Welsh JA, Le NA, et al. Dietary fructose reduction improves markers of cardiovascular disease risk in Hispanic-American adolescents with NAFLD. Nutrients 2014;6(8):3187-3201.
27. Jameel F, Phang M, Wood LG, et al. Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation. Lipids Health Dis 2014;13:195.
28. Angelopoulos TJ, Lowndes J, Sinnett S, et al. Fructose Containing Sugars at Normal Levels of Consumption Do Not Effect Adversely Components of the Metabolic Syndrome and Risk Factors for Cardiovascular Disease. Nutrient 2016;8(4):179.
29. Johnston RD, Stephenson MC, Crossland H, et al. No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Gastroenterology 2013;145(5):1016-1025.e1012.
30. Silbernagel G, Machann J, Häring HU, et al. Plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, e-selectin and C-reactive protein levels in response to 4-week very-high-fructose or -glucose diets. Eur J Clin Nutr 2014;68(1):97-100.
31. Raatz SK, Johnson LK, Picklo MJ. Consumption of Honey, Sucrose, and High-Fructose Corn Syrup Produces Similar Metabolic Effects in Glucose-Tolerant and -Intolerant Individuals. J Nutr 2015;145(10):2265-2272.
32. Huang YS, Ogbechi J, Clanchy FI, et al. IDO and Kynurenine Metabolites in Peripheral and CNS Disorders. Front Immunol 2020;11(388).