Quercetin'in 3T3-L1 adipositlerinde lipid birikimi ve adiponektin düzeyi üzerindeki etkisinin araştırılması
Year 2025,
Volume: 18 Issue: 1, 17 - 17
Gizem Akan
,
Melek Tunç Ata
,
Emine Kılıç Toprak
Abstract
Amaç: Obezite, adipoz dokunun homeostazını bozarak adipoz hücrelerinin sayısında ve büyüklüğünde artışa neden olur. Literatürde quercetin polifenolünün çeşitli mekanizmalar aracılığıyla sağlık üzerinde pek çok olumlu etkileri bilinmektedir. Araştırmamızın amacı, quercetinin olgun ve hipertrofik adipositlerde lipit birikimi ve adiponektin (ADP) seviyeleri üzerindeki etkilerini araştırmaktır.
Gereç ve yöntem: Çalışmada, 3T3-L1 preadiposit hücreler farklılaştırıldıktan sonra yüksek glikoz içeren ortamda 8 gün muamele edilerek olgun adipositler, 18 gün muamele edilerek ise hipertrofik adipositler elde edildi. Quercetin (40 ve 80 µM), olgun adipositlere 24 saat, hipertrofik adipositlere ise 48 saat boyunca uygulandı. Oil-Red-O boyama yöntemiyle lipit miktarı görüntülendi. ELISA yöntemi aracılığıyla lipit birikimi ve ADP seviyesi ölçüldü. İstatistiksel analiz için; tek yönlü varyans analizi (post hoc: Tukey testi) kullanıldı. P≤0,05 değeri istatistiksel olarak anlamlı kabul edildi.
Bulgular: Olgun adipositlere her iki quercetin dozunun uygulaması lipit birikimini anlamlı olarak azalttı (p≤0.05). Olgun adipositlerde 80 µM quercetin uygulaması, ADP seviyelerinde anlamlı bir artışa yol açtı (p≤0,05). Hipertrofik adipositlere quercetin uygulaması ise, ADP seviyelerinde anlamlı bir azalmaya yol açtı (p≤0,05).
Sonuç: Çalışmamız, quercetinin olgun adipositlerde lipit birikimini azaltıp ADP seviyesini artırdığını ortaya koydu. Ancak, hipertrofik adipositlerde ise quercetinin lipit birikiminde anlamlı bir etkisi olmayıp ADP seviyesini azalttığı gözlendi. Bu bulgular, quercetinin obezitenin erken döneminde sağlık üzerindeki koruyucu etkilerini ortaya koymakla birlikte, obezitenin daha ileri döneminde etkinliğinin sınırlı kaldığını göstermektedir.
Ethical Statement
bu çalışma hücre kültürü çalışması olup, etik kurul izin belgesi gerekmemektedir
Supporting Institution
PAU Bilimsel Araştırmalar Koordinatörlüğü (Proje No: 2023SABE009)
Thanks
Dr. Öğr. Üyesi Hande Şenol'a istatistiksel analizlerdeki yardımları için teşekkür ediyoruz
References
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- Herranz López M, Borrás Linares I, Olivares Vicente M, Gálvez J, Segura Carretero A, Micol V. Correlation between the cellular metabolism of quercetin and its glucuronide metabolite and oxidative stress in hypertrophied 3T3-L1 adipocytes. Phytomedicine. 2017;25:25-28. doi:10.1016/j.phymed.2016.12.008
- Herranz López M, OlivaresVicente M, Rodríguez Gallego E, et al. Quercetin metabolites from Hibiscus sabdariffa contribute to alleviate glucolipotoxicity-induced metabolic stress in vitro. Food Chem Toxicol. 2020;144:111606. doi:10.1016/j.fct.2020.111606
- Herranz López M, Fernández Arroyo S, Pérez Sanchez A, et al. Synergism of plant-derived polyphenols in adipogenesis: perspectives and implications. Phytomedicine. 2012;19(3-4):253-261. doi:10.1016/j.phymed.2011.12.001
- Yeop Han C, Kargi AY, Omer M, et al. Differential effect of saturated and unsaturated free fatty acids on the generation of monocyte adhesion and chemotactic factors by adipocytes: dissociation of adipocyte hypertrophy from inflammation. Diabetes. 2010;59(2):386-396. doi:10.2337/db09-0925
- Cave E, Crowther NJ. The Use of 3T3-L1 Murine Preadipocytes as a Model of Adipogenesis. Methods Mol Biol. 2019;1916:263-272. doi:10.1007/978-1-4939-8994-2_25
- Li T, Zhang L, Jin C, Xiong Y, Cheng YY, Chen K. Pomegranate flower extract bidirectionally regulates the proliferation, differentiation and apoptosis of 3T3-L1 cells through regulation of PPARγ expression mediated by PI3K-AKT signaling pathway. Biomed Pharmacother. 2020;131:110769. doi:10.1016/j.biopha.2020.110769
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- Tung YC, Hsieh PH, Pan MH, Ho CT. Cellular models for the evaluation of the antiobesity effect of selected phytochemicals from food and herbs. J Food Drug Anal. 2017;25(1):100-110. doi:10.1016/j.jfda.2016.10.018
- D'Andrea G. Quercetin: A flavonol with multifaceted therapeutic applications?. Fitoterapia. 2015;106:256-271. doi:10.1016/j.fitote.2015.09.018
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- Ting Y, Chang WT, Shiau DK, Chou PH, Wu MF, Hsu CL. Antiobesity Efficacy of Quercetin-Rich Supplement on Diet-Induced Obese Rats: Effects on Body Composition, Serum Lipid Profile, and Gene Expression. J Agric Food Chem. 2018;66(1):70-80. doi:10.1021/acs.jafc.7b03551
- Govindaraj J, Govindaraj K, Jayesh SR, Padmavathy K, Ramalingam M, U V. Role of adipokines in obesity and obesity-related metabolic disorders. Res J Pharm Technol. 2021;14(4261-4264). doi:10.52711/0974-360X.2021.00739
- Prieto Hontoria PL, Fernández Galilea M, Pérez Matute P, Martínez JA, Moreno Aliaga MJ. Lipoic acid inhibits adiponectin production in 3T3-L1 adipocytes. J Physiol Biochem. 2013;69(3):595-600. doi:10.1007/s13105-012-0230-7
- Tzeng YM, Chen K, Rao YK, Lee MJ. Kaempferitrin activates the insulin signaling pathway and stimulates secretion of adiponectin in 3T3-L1 adipocytes. Eur J Pharmacol. 2009;607(1-3):27-34. doi:10.1016/j.ejphar.2009.01.023
- Ahmed QU, Sarian MN, Mat So'ad SZ, et al. Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study. Biomolecules. 2018;8(4):149. Published 2018 Nov 15. doi:10.3390/biom8040149
- Sannappa Gowda NG, Shiragannavar VD, Karunakara SH, et al. Novel role of Quercetin in ameliorating metabolic syndrome via VDR mediated activation of adiponectin/AdipoR2 signaling. Biochem Biophys Rep. 2024;39:101754. Published 2024 Jun 21. doi:10.1016/j.bbrep.2024.101754
- Noori Z, Sharifi M, Dastghaib S, et al. Quercetin declines LPS induced inflammation and augments adiponectin expression in 3T3-L1 differentiated adipocytes SIRT-1 dependently. Mol Biol Rep. 2024;51(1):445. Published 2024 Mar 23. doi:10.1007/s11033-024-09334-7
- Hwang JT, Kwon DY, Yoon SH. AMP-activated protein kinase: a potential target for the diseases prevention by natural occurring polyphenols. N Biotechnol. 2009;26(1-2):17-22. doi:10.1016/j.nbt.2009.03.005
Investigation of the effect of quercetin on the accumulation of lipids and the level of adiponectin in 3T3-L1 adipocytes
Year 2025,
Volume: 18 Issue: 1, 17 - 17
Gizem Akan
,
Melek Tunç Ata
,
Emine Kılıç Toprak
Abstract
Purpose: Obesity disrupts the homeostasis of adipose tissue, leading to an increase in the number and size of adipose cells. Many positive effects of quercetin polyphenol on health through various mechanisms are known in the literature. The aim of our study was to investigate the effects of quercetin on lipid accumulation and adiponectin (ADP) levels in mature and hypertrophic adipocytes.
Materials and methods: In this study, 3T3-L1 differentiated preadipocyte cells were exposed to high glucose media for 8 days to generate mature adipocytes, then for 18 days to produce hypertrophic adipocytes. Quercetin (40 and 80 µM) was administered to mature adipocytes for 24 hours and to hypertrophic adipocytes for 48 hours. Lipid content was visualized by Oil-Red-O staining method. Lipid accumulation and ADP level were measured by ELISA method. For statistical analysis, one-way analysis of variance (post hoc: Tukey test) was used. P≤0.05 was considered statistically significant.
Results: The administration of both quercetin doses to mature adipocytes significantly reduced lipid accumulation (p≤0.05). The administration of 80 µM quercetin in mature adipocytes caused a significant increase in ADP levels (p≤0.05). Administration of quercetin to hypertrophic adipocytes caused a significant decrease in ADP levels (p≤0.05).
Conclusion: Our study revealed that quercetin decreased lipid accumulation and increased ADP levels in mature adipocytes. However, in hypertrophic adipocytes, quercetin had no significant effect on lipid accumulation and decreased ADP levels. These findings suggest that quercetin has protective effects on health in the early stages of obesity, but its efficacy is limited in the later stages of obesity.
Ethical Statement
The study is a cell culture study that does not require ethics committee approval.
Supporting Institution
This study was supported by PAU Scientific Research Projects Coordination Unit (Project No: 2023SABE009).
Thanks
The authors thank Asst. Prof. Hande Senol for her help in statistical analyses.
References
- Kopelman PG. Obesity as a medical problem. Nature. 2000;404(6778):635-643. doi:10.1038/35007508
- Oates EH, Antoniewicz MR. Coordinated reprogramming of metabolism and cell function in adipocytes from proliferation to differentiation. Metab Eng. 2022;69:221-230. doi:10.1016/j.ymben.2021.12.005
- Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006;444(7121):847-853. doi:10.1038/nature05483
- Hwang JT, Park IJ, Shin JI, et al. Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun. 2005;338(2):694-699. doi:10.1016/j.bbrc.2005.09.195
- Rayalam S, Yang JY, Ambati S, DellaFera MA, Baile CA. Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res. 2008;22(10):1367-1371. doi:10.1002/ptr.2503
- Ahn J, Lee H, Kim S, Park J, Ha T. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways [published correction appears in Biochem Biophys Res Commun. 2011 Jan 7;404(1):579]. Biochem Biophys Res Commun. 2008;373(4):545-549. doi:10.1016/j.bbrc.2008.06.077
- Yahfoufi N, Alsadi N, Jambi M, Matar C. The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients. 2018;10(11):1618. Published 2018 Nov 2. doi:10.3390/nu10111618
- Herranz López M, Borrás Linares I, Olivares Vicente M, Gálvez J, Segura Carretero A, Micol V. Correlation between the cellular metabolism of quercetin and its glucuronide metabolite and oxidative stress in hypertrophied 3T3-L1 adipocytes. Phytomedicine. 2017;25:25-28. doi:10.1016/j.phymed.2016.12.008
- Herranz López M, OlivaresVicente M, Rodríguez Gallego E, et al. Quercetin metabolites from Hibiscus sabdariffa contribute to alleviate glucolipotoxicity-induced metabolic stress in vitro. Food Chem Toxicol. 2020;144:111606. doi:10.1016/j.fct.2020.111606
- Herranz López M, Fernández Arroyo S, Pérez Sanchez A, et al. Synergism of plant-derived polyphenols in adipogenesis: perspectives and implications. Phytomedicine. 2012;19(3-4):253-261. doi:10.1016/j.phymed.2011.12.001
- Yeop Han C, Kargi AY, Omer M, et al. Differential effect of saturated and unsaturated free fatty acids on the generation of monocyte adhesion and chemotactic factors by adipocytes: dissociation of adipocyte hypertrophy from inflammation. Diabetes. 2010;59(2):386-396. doi:10.2337/db09-0925
- Cave E, Crowther NJ. The Use of 3T3-L1 Murine Preadipocytes as a Model of Adipogenesis. Methods Mol Biol. 2019;1916:263-272. doi:10.1007/978-1-4939-8994-2_25
- Li T, Zhang L, Jin C, Xiong Y, Cheng YY, Chen K. Pomegranate flower extract bidirectionally regulates the proliferation, differentiation and apoptosis of 3T3-L1 cells through regulation of PPARγ expression mediated by PI3K-AKT signaling pathway. Biomed Pharmacother. 2020;131:110769. doi:10.1016/j.biopha.2020.110769
- Blüher M, Aras M, Aronne LJ, et al. New insights into the treatment of obesity. Diabetes Obes Metab. 2023;25(8):2058-2072. doi:10.1111/dom.15077
- Ruiz Ojeda FJ, Rupérez AI, Gomez Llorente C, Gil A, Aguilera CM. Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review. Int J Mol Sci. 2016;17(7):1040. Published 2016 Jun 30. doi:10.3390/ijms17071040
- Tung YC, Hsieh PH, Pan MH, Ho CT. Cellular models for the evaluation of the antiobesity effect of selected phytochemicals from food and herbs. J Food Drug Anal. 2017;25(1):100-110. doi:10.1016/j.jfda.2016.10.018
- D'Andrea G. Quercetin: A flavonol with multifaceted therapeutic applications?. Fitoterapia. 2015;106:256-271. doi:10.1016/j.fitote.2015.09.018
- Yang JY, Della Fera MA, Rayalam S, et al. Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci. 2008;82(19-20):1032-1039. doi:10.1016/j.lfs.2008.03.003
- Eseberri I, Miranda J, Lasa A, et al. Effects of Quercetin Metabolites on Triglyceride Metabolism of 3T3-L1 Preadipocytes and Mature Adipocytes. Int J Mol Sci. 2019;20(2):264. Published 2019 Jan 11. doi:10.3390/ijms20020264
- Perdicaro DJ, Rodriguez Lanzi C, Gambarte Tudela J, Miatello RM, Oteiza PI, Vazquez Prieto MA. Quercetin attenuates adipose hypertrophy, in part through activation of adipogenesis in rats fed a high-fat diet. J Nutr Biochem. 2020;79:108352. doi:10.1016/j.jnutbio.2020.108352
- Ting Y, Chang WT, Shiau DK, Chou PH, Wu MF, Hsu CL. Antiobesity Efficacy of Quercetin-Rich Supplement on Diet-Induced Obese Rats: Effects on Body Composition, Serum Lipid Profile, and Gene Expression. J Agric Food Chem. 2018;66(1):70-80. doi:10.1021/acs.jafc.7b03551
- Govindaraj J, Govindaraj K, Jayesh SR, Padmavathy K, Ramalingam M, U V. Role of adipokines in obesity and obesity-related metabolic disorders. Res J Pharm Technol. 2021;14(4261-4264). doi:10.52711/0974-360X.2021.00739
- Prieto Hontoria PL, Fernández Galilea M, Pérez Matute P, Martínez JA, Moreno Aliaga MJ. Lipoic acid inhibits adiponectin production in 3T3-L1 adipocytes. J Physiol Biochem. 2013;69(3):595-600. doi:10.1007/s13105-012-0230-7
- Tzeng YM, Chen K, Rao YK, Lee MJ. Kaempferitrin activates the insulin signaling pathway and stimulates secretion of adiponectin in 3T3-L1 adipocytes. Eur J Pharmacol. 2009;607(1-3):27-34. doi:10.1016/j.ejphar.2009.01.023
- Ahmed QU, Sarian MN, Mat So'ad SZ, et al. Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study. Biomolecules. 2018;8(4):149. Published 2018 Nov 15. doi:10.3390/biom8040149
- Sannappa Gowda NG, Shiragannavar VD, Karunakara SH, et al. Novel role of Quercetin in ameliorating metabolic syndrome via VDR mediated activation of adiponectin/AdipoR2 signaling. Biochem Biophys Rep. 2024;39:101754. Published 2024 Jun 21. doi:10.1016/j.bbrep.2024.101754
- Noori Z, Sharifi M, Dastghaib S, et al. Quercetin declines LPS induced inflammation and augments adiponectin expression in 3T3-L1 differentiated adipocytes SIRT-1 dependently. Mol Biol Rep. 2024;51(1):445. Published 2024 Mar 23. doi:10.1007/s11033-024-09334-7
- Hwang JT, Kwon DY, Yoon SH. AMP-activated protein kinase: a potential target for the diseases prevention by natural occurring polyphenols. N Biotechnol. 2009;26(1-2):17-22. doi:10.1016/j.nbt.2009.03.005