TY  - JOUR
T1  - Investigation of the effect of quercetin on the accumulation of lipids and the level of adiponectin in 3T3-L1 adipocytes
TT  - Quercetin'in 3T3-L1 adipositlerinde lipid birikimi ve adiponektin düzeyi üzerindeki etkisinin araştırılması
AU  - Kılıç Toprak, Emine
AU  - Akan, Gizem
AU  - Tunç Ata, Melek
PY  - 2025
DA  - January
Y2  - 2024
DO  - 10.31362/patd.1578749
JF  - Pamukkale Medical Journal
JO  - Pam Tıp Derg
PB  - Pamukkale Üniversitesi
WT  - DergiPark
SN  - 1308-0865
SP  - 179
EP  - 187
VL  - 18
IS  - 1
LA  - en
AB  - AbstractPurpose: Obesity disrupts the homeostasis of adipose tissue, leading to an increase in the number and size ofadipose cells. Many positive effects of quercetin polyphenol on health through various mechanisms are knownin the literature. The aim of our study was to investigate the effects of quercetin on lipid accumulation andadiponectin (ADP) levels in mature and hypertrophic adipocytes.Materials and methods: In this study, 3T3-L1 differentiated preadipocyte cells were exposed to high glucosemedia 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 48hours. Lipid content was visualized by Oil-Red-O staining method. Lipid accumulation and ADP level weremeasured by ELISA method. For statistical analysis, one-way analysis of variance (post hoc: Tukey test) wasused. p≤0.05 was considered statistically significant.Results: The administration of both quercetin doses to mature adipocytes significantly reduced lipid accumulation(p=0.0001). The administration of 80 μM quercetin in mature adipocytes caused a significant increase in ADPlevels (p=0.0001). Administration of quercetin to hypertrophic adipocytes caused a significant decrease in ADPlevels (p=0.0001).Conclusion: Our study revealed that quercetin decreased lipid accumulation and increased ADP levels inmature adipocytes. However, in hypertrophic adipocytes, quercetin had no significant effect on lipid accumulationand decreased ADP levels. These findings suggest that quercetin has protective effects on health in the earlystages of obesity, but its efficacy is limited in the later stages of obesity.
KW  - Adiponectin
KW  - adipocyte
KW  - lipid accumulation
KW  - obesity
KW  - quercetin.
N2  - Amaç: Obezite, adipoz dokunun homeostazını bozarak adipoz hücrelerinin sayısında ve büyüklüğünde artışaneden olur. Literatürde quercetin polifenolünün çeşitli mekanizmalar aracılığıyla sağlık üzerinde pek çokolumlu etkileri bilinmektedir. Araştırmamızın amacı, quercetinin olgun ve hipertrofik adipositlerde lipit birikimi veadiponektin (ADP) seviyeleri üzerindeki etkilerini araştırmaktır.Gereç ve yöntem: Çalışmada, 3T3-L1 preadiposit hücreler farklılaştırıldıktan sonra yüksek glikoz içerenortamda 8 gün muamele edilerek olgun adipositler, 18 gün muamele edilerek ise hipertrofik adipositler eldeedildi. Quercetin (40 ve 80 μM), olgun adipositlere 24 saat, hipertrofik adipositlere ise 48 saat boyuncauygulandı. Oil-Red-O boyama yöntemiyle lipit miktarı görüntülendi. ELISA yöntemi aracılığıyla lipit birikimi veADP seviyesi ölçüldü. İstatistiksel analiz için; tek yönlü varyans analizi (post hoc: Tukey testi) kullanıldı. p≤0,05değeri istatistiksel olarak anlamlı kabul edildi.Bulgular: Olgun adipositlere her iki quercetin dozunun uygulaması lipit birikimini anlamlı olarak azalttı(p=0,0001). Olgun adipositlerde 80 μM quercetin uygulaması, ADP seviyelerinde anlamlı bir artışa yol açtı(p=0,0001). Hipertrofik adipositlere quercetin uygulaması ise, ADP seviyelerinde anlamlı bir azalmaya yol açtı(p=0,0001).Sonuç: Çalışmamız, quercetinin olgun adipositlerde lipit birikimini azaltıp ADP seviyesini artırdığını ortayakoydu. Ancak, hipertrofik adipositlerde ise quercetinin lipit birikiminde anlamlı bir etkisi olmayıp ADP seviyesiniazalttığı gözlendi. Bu bulgular, quercetinin obezitenin erken döneminde sağlık üzerindeki koruyucu etkileriniortaya koymakla birlikte, obezitenin daha ileri döneminde etkinliğinin sınırlı kaldığını göstermektedir.
CR  - Kopelman PG. Obesity as a medical problem. Nature. 2000;404(6778):635-643. doi:10.1038/35007508
CR  - 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
CR  - Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006;444(7121):847-853. doi:10.1038/nature05483
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - D'Andrea G. Quercetin: A flavonol with multifaceted therapeutic applications?. Fitoterapia. 2015;106:256-271. doi:10.1016/j.fitote.2015.09.018
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
CR  - 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
UR  - https://doi.org/10.31362/patd.1578749
L1  - https://dergipark.org.tr/tr/download/article-file/4337433
ER  -