Effect of quercetin on perirenal adipose tissue adiponectin and resistin levels in rats with metabolic syndrome induced by high fructose-diet

Yıl 2024, Cilt: 17 Sayı: 2, 347 - 357, 01.04.2024

Emine Kılıç Toprak , Melek Tunç Ata

https://doi.org/10.31362/patd.1398168

Öz

Purpose: Metabolic syndrome (MetS) is a cluster of risk factors for developing heart disease, stroke, and type 2 diabetes. Visceral adiposity and insulin resistance are crucial mechanisms of MetS. The increase in adipose tissue observed in MetS causes proinflammatory and anti-inflammatory cytokine imbalance. Accumulating evidence on quercetin, one of the antioxidants frequently used in MetS treatment, suggests that quercetin has significant anti-obesity and lipid-lowering effects simultaneously. Our aim is to investigate the effects of quercetin supplementation on MetS parameters and adipose tissue adipokine levels in rats fed high fructose.
Materials and methods: Sprague Dawley rats, 8-10 weeks of age, were divided into 4 groups, including a control group (C), high fructose (HF) group, quercetin (Q) group, and high fructose+quercetin (HF+Q) group. Fructose was administered to HF groups as a 20% solution in drinking water for 10 weeks. The rats in the Q groups were given 50 mg quercetin per kg BW by gavage for the last 4 weeks of experiment. The body weight, triglyceride (TG), high density lipoprotein (HDL), fasting insulin, fasting glucose, and HOMA-IR were determined in rats. Adiponectin and resistin levels were determined by ELISA assay from perirenal adipose tissue homogenates.
Results: We showed that quercetin acts to improve TG, fasting glucose and insulin resistance in high fructose-fed rats. In this study, we found no effect of quercetin on perirenal adipose tissue adiponectin and resistin levels.
Conclusion: These results showed that high fructose could induce MetS in rats, while quercetin could favorably affect these parameters.

Anahtar Kelimeler

Metabolic syndrome, quercetin, perirenal adipose tissue, adiponectin, resistin

Etik Beyan

" (PAUHDEK-2023/31)" konulu çalışmanız 19.10.2023 tarih ve 2023/06 sayılı toplantı

Destekleyen Kurum

Pamukkale Üniversitesi BİLİMSEL ARAŞTIRMA PROJELERİ KOORDİNATÖRLÜĞÜ

Proje Numarası

2019HZDP015

Yüksek fruktozlu diyet ile metabolik sendrom oluşturulmuş sıçanlarda quercetin'in perirenal yağ dokusu adiponektin ve resistin düzeyleri üzerine etkisi

Öz

Amaç: Metabolik sendrom (MetS) kalp hastalığı, inme ve tip 2 diyabet gelişimi için bir risk faktörleri kümesidir. Visseral adipozite ve insülin direnci MetS'in önemli mekanizmalarıdır. MetS’de gözlenen yağ dokusu artışı proinflamatuar ve antiinflamatuar sitokin dengesizliğine neden olur. MetS tedavisinde sıklıkla kullanılan antioksidanlardan biri olan quercetin hakkındaki kanıtlar, quercetin'in önemli anti-obezite ve lipid düşürücü etkilerinin eş zamanlı olduğu gösterilmiştir. Amacımız, yüksek fruktozla beslenen sıçanlarda quercetin takviyesinin MetS parametreleri ve yağ doku adipokin düzeyleri üzerindeki etkilerini araştırmaktır.
Gereç ve yöntem: 8-10 haftalık Sprague Dawley sıçanlar, kontrol grubu (C), yüksek fruktoz (HF) grubu, quercetin (Q) grubu ve yüksek fruktoz+quercetin (HF+Q) grubu olmak üzere 4 gruba ayrıldı. Fruktoz, HF grup sıçanlarına içme suyunda %20'lik çözelti halinde 10 hafta süreyle uygulandı. Quercetin grubundaki sıçanlara deneyin son 4 haftasında vücut ağırlığı kg başına 50 mg quercetin gavaj yoluyla verildi. Sıçanlarda vücut ağırlığı, trigliserit (TG), yüksk dansiteli lipoprotein (HDL), açlık insülini, açlık glukozu ve HOMA-IR belirlendi. Adiponektin ve resistin seviyeleri perirenal yağ dokusu homojenatlarından ELISA yöntemi ile belirlendi.
Bulgular: Yüksek fruktozla beslenen sıçanlarda quercetin'in TG'yi, açlık glikozunu ve insülin direncini iyileştirdiğini gösterdik. Bu çalışmada quercetin'in, perirenal yağ dokusu adiponektin ve resistin düzeylerine etkisi bulunmadı.
Sonuç: Bu sonuçlar, yüksek fruktozun sıçanlarda MetS’i indükleyebileceğini, quercetin’in ise bu parametreleri olumlu yönde etkileyebileceğini göstermektedir.

Anahtar Kelimeler

Metabolik sendrom, quercetin, perirenal adipoz doku, adiponektin, resistin

Proje Numarası

2019HZDP015

Kaynakça

• 1. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365:1415-1428. https://doi.org/10.1016/S0140-6736(05)66378-7
• 2. Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120:1640-1645. https://doi.org/10.1161/CIRCULATIONAHA.109.192644
• 3. Hu J, Yang S, Zhang A, et al. Abdominal obesity ıs more closely associated with diabetic kidney disease than general obesity. Diabetes Care 2016;39:179-180. https://doi.org/10.2337/dc16-1025
• 4. Fan H, Li X, Zheng L, et al. Abdominal obesity is strongly associated with Cardiovascular Disease and its Risk Factors in Elderly and very Elderly Community-dwelling Chinese. Sci Rep 2016;6:21521. https://doi.org/10.1038/srep21521
• 5. Kobayashi K, Inoguchi T. Adipokines: therapeutic targets for metabolic syndrome. Curr Drug Targets 2005;6:525-529. https://doi.org/10.2174/1389450054021972
• 6. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006;116:1784-1792. https://doi.org/10.1172/JCI2912
• 7. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271:10697-10703. https://doi.org/10.1074/jbc.271.18.10697
• 8. Mohammadzadeh G, Zarghami N, Mobaseri M. Serum resistin concentration in obese diabetic patients: any possible relation to insulin resistance indices? Int J Endocrinol Metab 2008;4:183-193.
• 9. Schöttker B, Herder C, Rothenbacher D, Roden M, Kolb H, Müller H, Brenner H. Proinflammatory cytokines, adiponectin, and increased risk of primary cardiovascular events in diabetic patients with or without renal dysfunction: results from the ESTHER study. Diabetes Care 2013;36:1703-1711. https://doi.org/10.2337/dc12-1416
• 10. Zorena K, Jachimowicz Duda O, Ślęzak D, Robakowska M, Mrugacz M. Adipokines and obesity. potential link to metabolic disorders and chronic complications. Int J Mol Sci 2020;21:3570(e1-18). https://doi.org/10.3390/ijms21103570
• 11. Leiherer A, Stoemmer K, Muendlein A, et al. Quercetin impacts expression of metabolism- and obesity-associated genes in SGBS adipocytes. Nutrients 2016;8:282(e1-12). https://doi.org/10.3390/nu8050282
• 12. Yamamoto Y, Oue E. Antihypertensive effect of quercetin in rats fed with a high-fat high-sucrose diet. Biosci Biotechnol Biochem 2006;70:933-939. https://doi.org/10.1271/bbb.70.933
• 13. Dong Q, Chen L, Lu Q, et al. Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression. Br J Pharmacol 2014;171:4440-4454. https://doi.org/10.1111/bph.12795
• 14. Aguirre L, Arias N, Teresa Macarulla M, Gracia A, P Portillo M. Beneficial effects of quercetin on obesity and diabetes. The Open Nutraceuticals Journal 2011;4:189-198. https://doi.org/10.2174/1876396001104010189
• 15. Bhaskar S, Kumar KS, Krishnan K, Antony H. Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits. Nutrition 2013;29:219-229. https://doi.org/10.1016/j.nut.2012.01.019
• 16. Hosseini A, Razavi BM, Banach M, Hosseinzadeh H. Quercetin and metabolic syndrome: a review. Phytother Res 2021;35:5352-5364. https://doi.org/10.1002/ptr.7144
• 17. Zhao L, Zhang Q, Ma W, Tian F, Shen H, Zhou M. A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota. Food Funct 2017;8:4644-4656. https://doi.org/10.1039/c7fo01383c
• 18. Dong J, Zhang X, Zhang L, et al. Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKα1/SIRT1. J Lipid Res 2014;55:363-374. https://doi.org/10.1194/jlr.M038786
• 19. Lee KW, Kim YJ, Kim DO, Lee HJ, Lee CY. Major phenolics in apple and their contribution to the total antioxidant capacity. J Agric Food Chem 2003;51:6516-6520. https://doi.org/10.1021/jf034475w
• 20. Yang L, Li XF, Gao L, Zhang YO, Cai GP. Suppressive effects of quercetin-3-O-(6″-Feruloyl)-β-D-galactopyranoside on adipogenesis in 3T3-L1 preadipocytes through down-regulation of PPARγ and C/EBPα expression. Phytother Res 2012;26:438-444. https://doi.org/10.1002/ptr.3604
• 21. Pfeuffer M, Auinger A, Bley U, et al. Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms. Nutr Metab Cardiovasc Dis 2013;23:403-409. https://doi.org/10.1016/j.numecd.2011.08.010
• 22. Vazquez Prieto MA, Bettaieb A, Rodriguez Lanzi C, et al. Catechin and quercetin attenuate adipose inflammation in fructose-fed rats and 3T3-L1 adipocytes. Mol Nutr Food Res 2015;59:622-633. https://doi.org/10.1002/mnfr.201400631
• 23. Panchal SK, Poudyal H, Brown L. Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. J Nutr 2012;142:1026-1032. https://doi.org/10.3945/jn.111.157263
• 24. Wein S, Behm N, Petersen RK, Kristiansen K, Wolffram S. Quercetin enhances adiponectin secretion by a PPAR-gamma independent mechanism. Eur J Pharm Sci 2010;41:16-22. https://doi.org/10.1016/j.ejps.2010.05.004
• 25. Aranaz P, Zabala M, Romo Hualde A, et al. A combination of borage seed oil and quercetin reduces fat accumulation and improves insulin sensitivity in obese rats. Food Funct 2020;11:4512-4524. https://doi.org/10.1039/d0fo00504e 26. Jung CH, Cho I, Ahn J, Jeon TI, Ha TY. Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes. Phytother Res 2013;27:139-143. https://doi.org/10.1002/ptr.4687
• 27. Rivera L, Morón R, Zarzuelo A, Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol 2009;77:1053-1063. https://doi.org/10.1016/j.bcp.2008.11.027
• 28. Arias N, Picó C, Teresa Macarulla M, et al. A combination of resveratrol and quercetin induces browning in white adipose tissue of rats fed an obesogenic diet. Obesity (Silver Spring) 2017;25:111-121. https://doi.org/10.1002/oby.21706
• 29. Peredo Escárcega AE, Guarner Lans V, Pérez Torres I, et al. The combination of resveratrol and quercetin attenuates metabolic syndrome in rats by modifying the serum fatty acid composition and by upregulating SIRT 1 and SIRT 2 expression in white adipose tissue. Evid Based Complement Alternat Med 2015;2015:474032(e1-10). https://doi.org/10.1155/2015/474032
• 30. Wang M, Mao Y, Wang B, et al. Quercetin Improving Lipid Metabolism by Regulating Lipid Metabolism Pathway of Ileum Mucosa in Broilers. Oxid Med Cell Longev 2020;2020:8686248(e1-17). https://doi.org/10.1155/2020/8686248
• 31. Henagan TM, Cefalu WT, Ribnicky DM, et al. In vivo effects of dietary quercetin and quercetin-rich red onion extract on skeletal muscle mitochondria, metabolism, and insulin sensitivity. Genes Nutr 2015;10:451(e1-12). https://doi.org/10.1007/s12263-014-0451-1
• 32. Jespersen NZ, Feizi A, Andersen ES, et al. Heterogeneity in the perirenal region of humans suggests presence of dormant brown adipose tissue that contains brown fat precursor cells. Mol Metab 2019;24:30-43. https://doi.org/10.1016/j.molmet.2019.03.005
• 33. Liu BX, Sun W, Kong XQ. Perirenal fat: a unique fat pad and potential target for cardiovascular disease. Angiology 2019;70:584-593. https://doi.org/10.1177/0003319718799967
• 34. Yu H, Chhabra KH, Thompson Z, et al. Hypothalamic POMC deficiency increases circulating adiponectin despite obesity. Mol Metab 2020;35:100957. https://doi.org/10.1016/j.molmet.2020.01.021
• 35. Stewart LK, Wang Z, Ribnicky D, Soileau JL, Cefalu WT, Gettys TW. Failure of dietary quercetin to alter the temporal progression of insulin resistance among tissues of C57BL/6J mice during the development of diet-induced obesity. Diabetologia 2009;52:514-523. https://doi.org/10.1007/s00125-008-1252-0
• 36. Kim OY, Lee SM, Do H, et al. Influence of quercetin-rich onion peel extracts on adipokine expression in the visceral adipose tissue of rats. Phytother Res 2012;26:432-437. https://doi.org/10.1002/ptr.3570
• 37. Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature 2001;409:307-312. https://doi.org/10.1038/35053000
• 38. Rajala MW, Qi Y, Patel HR, et al. Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes 2004;53:1671-1679. https://doi.org/10.2337/diabetes.53.7.1671
• 39. Steppan CM, Lazar MA. Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 2002;13:18-23. https://doi.org/10.1016/s1043-2760(01)00522-7
• 40. Iqbal N, Seshadri P, Stern L, et al. Serum resistin is not associated with obesity or insulin resistance in humans. Eur Rev Med Pharmacol Sci 2005;9:161-165.