Investigation of the possible relation of apelin, kynurenine and IL-4/IL-10/IL-12/ Tnf-α levels with clinical and metabolic parameters in obesity

Yıl 2023, Cilt: 16 Sayı: 2, 282 - 289, 05.04.2023

İkbal Cansu BARIŞ MOĞUL Yavuz DODURGA Ecem PARS UYGUR Güzin Fidan YAYLALI Zeliha AKDAĞ

https://doi.org/10.31362/patd.1247216

Öz

Purpose: Obesity is a medical condition caused by excess body fat that accumulates at a level that can have a detrimental impact on health. Altered glucose and lipid metabolism, low-grade chronic inflammation controbutes to the pathogenesis of obesity and obesity-related metabolic dysfunction. In our study, we purposed to specify the apelin, kynurenine, IL-4, IL-10, IL-12, TNF-α protein levels in obese individuals and healthy control groups, and to research the possible relationship between clinical parameters with the data to be obtained.
Materials and methods: The levels of apelin, kynurenine, IL-4, IL-10, IL-12, TNF-α in serum/plasma samples were determined with enzyme-linked immunosorbent assay. Absorbance of the samples were measured on a microplate reader spectrophotometrically at a wavelength of 450 nm.
Results: The levels of kynurenine, IL-4, and IL-12 in the serum were higher in control group than in obese patients (p=0.009, p=0.004, p=0.002, respectively). The levels of TNF- α, IL-10, and apelin did not differ substantially between the obese patients and the control group (p=0.277, p=0.711, p=0.472, respectively).
Conclusion: Inflammation and altered immune response are two important components of obesity. They play a significant part in the emergence of obesity-related metabolic disorders. Alterations in adipokine levels may lead to the occurence and maintenance of insulin resistance and systemic inflammation in obesity. The results demonstrate that kynurenine, IL-4, and IL-12 have a complex role in obesity and can be used as therapeutic targets.

Anahtar Kelimeler

Obesity, chronic inflammation apelin, kynurenine, TNF-α, IL-4/IL-10/IL-12

Obezitede apelin, kinürenin ve IL-4/IL-10/IL-12/Tnf-α düzeylerinin klinik ve metabolik parametrelerle olası ilişkisinin araştırılması

Öz

Amaç: Obezite, sağlığı olumsuz etkileyebilecek düzeyde biriken aşırı vücut yağının neden olduğu tıbbi bir durumdur. Değişen glikoz ve lipid metabolizması, düşük dereceli kronik inflamasyon, obezite ve obezite ile ilişkili metabolik disfonksiyonun patogenezinde rol oynar. Çalışmamızda obez hastalarda ve sağlıklı kontrol gruplarında apelin, kinurenin, IL-4, IL-10, IL-12, TNF-α serum protein düzeylerini belirlemeyi ve klinik parametreler ile arasındaki olası ilişkiyi araştırmayı amaçladık.
Gereç ve yöntem: Serum/plazma örneklerindeki apelin, kinurenin, IL-4, IL-10, IL-12, TNF-α seviyeleri, enzim bağlantılı immunosorbent testi ile ölçüldü. Numunelerin absorbansı, 450 nm dalga boyunda spektrofotometrik olarak bir mikroplaka okuyucu ile belirlendi.
Bulgular: Kontrol grubunun serumlarındaki Kinurenin, IL-4 ve IL-12 düzeylerinin obez hastalara oranla anlamlı düzeyde daha yüksek olduğu belirlenmiştir (sırasıyla p=0.009, p=0,004, p=0,002). TNF-α, IL-10 ve apelin düzeyleri değerlendirildiğinde ise obez hastalar ve kontrol grubu arasında anlamlı bir fark olmadığı tespit edilmiştir (sırasıyla p=0,277, p=0,711, p=0,472).
Sonuç: Enflamasyon ve değişmiş bağışıklık yanıtı obezitenin iki önemli bileşenidir. Bu bileşenler obeziteye bağlı metabolik hastalıkların oluşumunda önemli rol oynamaktadırlar. Adipokin düzeylerindeki değişiklikler, obezitede sistemik inflamasyonun gelişimine ve insülin direncinin sürdülmesine yol açabilir. Elde edilen sonuçlar, kinurenin, IL-4 ve IL-12'nin obezitede karmaşık bir role sahip olduğunu ve terapötik hedefler olarak kullanılabileceğini göstermektedir.

Anahtar Kelimeler

Obezite, kronik inflamasyon apelin, kinurenin, TNF-α, IL-4/IL-10/IL-12

Kaynakça

• 1. Obesity and overweight. WHO Available at: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed March 04, 2020
• 2. Wolowczuk I, Hennart B, Leloire A, et al. Tryptophan metabolism activation by indoleamine 2,3- dioxygenase in adipose tissue of obese women: an attempt to maintain immune homeostasis and vascular tone. Am J Physiol Regulatory Integr Comp Physiol 2012;303:135-143. https://doi.org/10.1152/ajpregu.00373.2011
• 3. Liu J, Liu M, Chen L. Novel pathogenesis: regulation of apoptosis by Apelin/APJ system. Acta Biochim Biophys Sin 2017;49:471-478. https://doi.org/10.1093/abbs/gmx035
• 4. Castan Laurell I, Dray C, Valet P. The therapeutic potentials of apelin in obesity-associated diseases. Mol Cell Endocrinol 2021;529:111278. https://doi.org/10.1016/j.mce.2021.111278
• 5. Palmer ES, Irwin N, O’Harte FPM. Potential therapeutic role for apelin and related peptides in diabetes: an update. Clin Med Insights Endocrinol Diabetes 2022;15:11795514221074680. https://doi.org/10.1177/11795514221074679
• 6. Soriguer F, Garrido Sanchez L, et al. Apelin levels are ıncreased in morbidly obese subjects with type 2 diabetes mellitus. Obes Surg 2009;19:1574-1580. https://doi.org/10.1007/s11695-009-9955-y
• 7. Skarsvik S, Ludvigsson J, Vaarala O. Aberrant regulation of interleukin-12 receptor 2 chain on type 1 cytokine stimulated T lymphocytes in type 1 diabetes. Immunology 2005;114:287-293. https://doi.org/10.1111/j.1365-2567.2004.02102.x
• 8. Mangge H, Schauenstein K, Stroedter L, Griesl A, Maerz W, Borkenstein M. Low grade inflammation in juvenile obesity and type 1 diabetes associated with early signs of atherosclerosis. Exp Clin Endocrinol Diabetes 2004;112:378-382. https://doi.org/10.1055/s-2004-821023
• 9. Solon Biet SM, Cogger VC, Pulpitel T, et al. Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control. Nat Metab 2019;1:532-545. https://doi.org/10.1038/s42255-019-0059-2
• 10. Mangge H, Summers K L, Meinitzer A, et al. Obesity-related dysregulation of the tryptophan kynurenine metabolism: role of age and parameters of the metabolic syndrome. Obesity 2014;22:195-201. https://doi.org/10.1002/oby.20491
• 11. Cussotto S, Delgado I, Anesi A, et al. Tryptophan metabolic pathways are altered in obesity and are associated with systemic inflammation. Front Immunol 2020;11:557. https://doi.org/10.3389/fimmu.2020.00557
• 12. Polyzos KA, Ovchinnikova O, Berg M. et al. Inhibition of indoleamine 2,3-dioxygenase promotes vascular inflammation and increases atherosclerosis in Apoe-/- mice. Cardiovascular Res 2015;106:295-302. https://doi.org/10.1093/cvr/cvv100
• 13. Laurans L, Venteclef N, Haddad Y, et al. Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health. Nat Med 2018;24:1113-1120. https://doi.org/10.1038/s41591-018-0060-4
• 14. Brandacher G, Hoeller E, Fuchs D, Weiss HG. Chronic immune activation underlies morbid obesity: is IDO a key player? Curr Drug Metab 2007;8:289-295. https://doi.org/10.2174/138920007780362590
• 15. Chen T, Zheng X, Ma X, et al. Tryptophan Predicts the Risk for Future Type 2 Diabetes. PLoS ONE 2016. https://doi.org/10.1371/journal.pone.0162192
• 16. Matsuoka K, Kato K, Takao T, et al. Concentrations of various tryptophan metabolites are higher in patients with diabetes mellitus than in healthy aged male adults. Diabetol Int 2016;8:69-75. https://doi.org/10.1007/s13340-016-0282-y
• 17. Oxenkrug, G.F. Increased Plasma levels of xanthurenic and kynurenic acids in type 2 diabetes. Mol Neurobiol 2015;52:805-810. https://doi.org/10.1007/s12035-015-9232-0
• 18. Rebnord EW, Strand E, Midttun O, et al. The kynurenine: tryptophan ratio as a predictor of incident type 2 diabetes mellitus in individuals with coronary artery disease. Diabetologia 2017;60:1712-1721. https://doi.org/10.1007/s00125-017-4329-9
• 19. Sulo G, Vollset S.E, Nygard O, et al. Neopterin and kynurenine tryptophan ratio as predictors of coronary events in older adults, the Hordaland Health Study. Int J Cardiol 2013;168:1435-1440. https://doi.org/10.1016/j.ijcard.2012.12.090
• 20. Munipally PK, Agraharm SG, Valavala VK, Gundae S, Turlapati NR. Evaluation of indoleamine 2,3-dioxygenase expression and kynurenine pathway metabolites levels in serum samples of diabetic retinopathy patients. Arch Physiol Biochem 2011;117:254-258. https://doi.org/10.3109/13813455.2011.623705
• 21. Li M, Kwok MK, Fong SSM, Schooling CM. Indoleamine 2,3-dioxygenase and ischemic heart disease: a mendelian randomization study. Sci Rep 2019;9:8491. https://doi.org/10.1038/s41598-019-44819-7
• 22. O’Harte FPM, Parthsarathy V, Hogg C, et al. Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged ınsulin releasing, glucose lowering and anorexic properties. Biochem Pharmacol 2017;146:165-173. https://doi.org/10.1016/j.bcp.2017.10.002
• 23. Attane C, Foussal C, Le Gonidec S, et al. Apelin treatment ıncreases complete fatty acid oxidation, mitochondrial oxidative capacity, and biogenesis in muscle of ınsulin-resistant mice. Diabetes 2012;61:310-320. https://doi.org/10.2337/db11-0100
• 24. Suganami T, Ogawa Y. Adipose tissue macrophages: Their role in adipose tissue remodeling. J Leukoc Biol 2010;88:33-39. https://doi.org/10.1189/jlb.0210072
• 25. Calcaterra V, De Amici M, Klersy C, et al. Adiponectin, IL-10 and metabolic syndrome in obese children and adolescents. Acta Biomed 2009;80:117-123.
• 26. Pereira S, Teixeira L, Aguilar E, et al. Modulation of adipose tissue inflammation by FOXP3+ Treg cells, IL-10, and TGF-β in metabolically healthy class III obese individuals. Nutrition 2013;30:784-790. https://doi.org/10.1016/j.nut.2013.11.023
• 27. Schmidt F.M, Weschenfelder J, Sander C, et al. Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS One 2015;10:e0121971. https://doi.org/10.1371/journal.pone.0121971
• 28. Arismendi E, Rivas E, Agustí A, et al. The systemic inflammome of severe obesity before and after bariatric surgery. PLoS One 2014;9:e107859. https://doi.org/10.1371/journal.pone.0107859
• 29. Esposito K, Pontillo A, Giugliano F, et al. Association of low interleukin-10 levels with the metabolic syndrome in obese women. J Clin Endocrinol Metab 2003;88:1055-1058. https://doi.org/10.1210/jc.2002-021437
• 30. Chen LX, Zhang SD, Zhu LL, Sun M. Association of metabolic syndrome with serum interleukin-10 and high sensitive C reactive protein(hs-CRP) in old men. 2008;33:970-974.
• 31. Arslan N, Erdur B, Aydın A. Hormones and cytokines in childhood obesity. Indian Pediatrics 2010;47:829-839. https://doi.org/10.1007/s13312-010-0142-y
• 32. Skarsvik S, Ludvigsson J, Vaarala O. Aberrant regulation of interleukin-12 receptor 2 chain on type 1 cytokine stimulated T lymphocytes in type 1 diabetes. Immunology 2005;114:287-293. https://doi.org/10.1111/j.1365-2567.2004.02102.x
• 33. Suárez Álvarez K, Solís Lozano L, Leon Cabrera S, et al. Serum IL-12 is increased in Mexican obese subjects and associated with lowgrade inflammation and obesity-related parameters. Mediators Inflamm, 2013:8. https://doi.org/10.1155/2013/967067
• 34. Nikołaju A, Karczewska Kupczewska M, Straczkowski M. Relationship between serum IL-12 and p40 subunit concentrations and lipid parameters in overweight and obese women. Metabolic Syndrome and Related Disorders 2015;13. https://doi.org/10.1089/met.2014.0164