Quercetin prevents adipogenesis by regulation of transcriptional factors and lipases in OP9 cells

Seo,Yun-Soo; Kang,Ok-Hwa; Kim,Sung-Bae; Mun,Su-Hyun; Kang,Da-Hye; Yang,Da-Wun; Choi,Jang-Gi; Lee,Young-Mi; Kang,Dae-Kil; Lee,Ho-Seog; Kwon,Dong-Yeul

doi:10.3892/ijmm.2015.2185

Quercetin prevents adipogenesis by regulation of transcriptional factors and lipases in OP9 cells

Authors:
- Yun-Soo Seo
- Ok-Hwa Kang
- Sung-Bae Kim
- Su-Hyun Mun
- Da-Hye Kang
- Da-Wun Yang
- Jang-Gi Choi
- Young-Mi Lee
- Dae-Kil Kang
- Ho-Seog Lee
- Dong-Yeul Kwon
View Affiliations

Affiliations: Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea, BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea
Published online on: April 15, 2015 https://doi.org/10.3892/ijmm.2015.2185
Pages: 1779-1785

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

With the industrialization of society, the increase in the prevalence of obesity and metabolic disorders has become an important health concern in a number of countries. Quercetin (3,30,40,5,7-pentahydroxyflavone) is well known as a bioactive flavonoid in a variety of biological resources. The aim of the present study was to explore the machanisms responsible for the anti-adipogenic activity of quercetin and its effects on the lipolysis in OP9 mouse stromal cells which rapidly differentiate into adipocytes. The differentiation of OP9 cells into adipocytes was evaluated by the measurement of lipid accumulation by Oil Red O (ORO) staining; lipid accumulation was significantly impaired by treatment with quercetin. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to measure the expression levels of CCAAT/enhancer binding protein α (C/EBPα), proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS). The mRNA expression levels of lipases, such as adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) were also measured by RT-PCR. Quercetin significantly decreased the expression of transcription factors, including C/EBPα, PPARγ and SREBP-1c both at the protein and mRNA level. The results from the present study demonstrate that quercetin prevents adipogenesis by upregulating ATGL and HSL expression and downregulating FAS, LPL and adipocyte fatty acid-binding protein (aP2) expression, as well as the expression of transcription factors. Our data suggest that quercetin has therapeutic potential by regulating the expression of transcriptional factors and enzymes associated with adipogenesis.

View Figures

View References

1	Kopelman PG: Obesity as a medical problem. Nature. 404:635–643. 2000.PubMed/NCBI
2	Isganaitis E and Lustig RH: Fast food, central nervous system insulin resistance, and obesity. Arterioscler Thromb Vasc Biol. 25:2451–2462. 2005. View Article : Google Scholar : PubMed/NCBI
3	Frühbeck G1, Gómez-Ambrosi J, Muruzábal FJ and Burrell MA: The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab. 280:E827–E847. 2001.PubMed/NCBI
4	Tang QQ, Jiang MS and Lane MD: Repressive effect of Sp1 on the C/EBP alpha gene promoter: role in adipocyte differentiation. Mol Cell Biol. 19:4855–4865. 1999.PubMed/NCBI
5	Gregoire FM, Smas CM and Sul HS: Understanding adipocyte differentiation. Physiol Rev. 78:783–809. 1998.PubMed/NCBI
6	Otto TC and Lane MD: Adipose development: from stem cell to adipocyte. Crit Rev Biochem Mol Biol. 40:229–242. 2005. View Article : Google Scholar : PubMed/NCBI
7	White UA and Stephens JM: Transcriptional factors that promote formation of white adipose tissue. Mol Cell Endocrinol. 318:10–14. 2010. View Article : Google Scholar
8	Eberlé D1, Hegarty B, Bossard P, Ferré P and Foufelle F: SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 86:839–848. 2004. View Article : Google Scholar : PubMed/NCBI
9	Griffin MJ and Sul HS: Insulin regulation of fatty acid synthase gene transcription: roles of USF and SREBP-1c. IUBMB Life. 56:595–600. 2004. View Article : Google Scholar
10	Lodhi IJ, Yin L, Jensen-Urstad AP, et al: Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARγ activation to decrease diet-induced obesity. Cell Metab. 16:189–201. 2012. View Article : Google Scholar : PubMed/NCBI
11	Benkalfat NB, Merzouk H, Bouanane S, et al: Altered adipose tissue metabolism in offspring of dietary obese rat dams. Clin Sci (Lond). 121:19–28. 2011. View Article : Google Scholar
12	Zimmermann R, Lass A, Haemmerle G and Zechner R: Fate of fat: the role of adipose triglyceride lipase in lipolysis. Biochim Biophys Acta. 1791:494–500. 2009. View Article : Google Scholar
13	Bezaire V, Mairal A, Ribet C, et al: Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes. J Biol Chem. 284:18282–18291. 2009. View Article : Google Scholar : PubMed/NCBI
14	Zimmermann R, Strauss JG, Haemmerle G, et al: Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science. 306:1383–1386. 2004. View Article : Google Scholar : PubMed/NCBI
15	Bischoff SC: Quercetin: potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care. 11:733–740. 2008. View Article : Google Scholar : PubMed/NCBI
16	Vicentini FT, Fonseca YM, Pitol DL, Iyomasa MM, Bentley MV and Fonseca MJ: Evaluation of protective effect of a water-in-oil microemulsion incorporating quercetin against UVB-induced damage in hairless mice skin. J Pharm Pharm Sci. 13:pp. 274–285. 2010, PubMed/NCBI
17	Wagner C, Vargas AP, Roos DH, et al: Comparative study of quercetin and its two glycoside derivatives quercetin and rutin against methylmercury (MgHg)-induced ROS production in rat brain slices. Arch Toxicol. 84:pp. 89–97. 2010, View Article : Google Scholar
18	Chen-yu G, Chun-fen Y, Qi-lu L, Qi T, Yan-wei X, Wei-na L and Guang-xi Z: Development of a quercetin-loaded nanostructured lipid carrier formulation for topical delivery. Int J Pharm. 430:292–298. 2012. View Article : Google Scholar : PubMed/NCBI
19	Ahn J, Lee H, Kim S, Park J and Ha T: The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun. 373:545–549. 2008. View Article : Google Scholar : PubMed/NCBI
20	Wolins NE, Quaynor BK, Skinner JR, Tzekov A, Park C, Choi K and Bickel PE: OP9 mouse stromal cells rapidly differentiate into adipocytes: characterization of a useful new model of adipogenesis. J Lipid Res. 47:450–460. 2006. View Article : Google Scholar
21	Rosen E, Eguchi J and Xu Z: Transcriptional targets in adipocyte biology. Expert Opin Ther Targets. 13:975–986. 2009. View Article : Google Scholar : PubMed/NCBI
22	Rosen ED and Spiegelman BM: Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol. 16:145–171. 2000. View Article : Google Scholar : PubMed/NCBI
23	Rosen ED, Walkey CJ, Puigserver P and Spiegelman BM: Transcriptional regulation of adipogenesis. Genes Dev. 14:1293–1307. 2000.PubMed/NCBI
24	Darlington GJ, Ross SE and MacDougald OA: The role of C/EBP genes in adipocyte differentiation. J Biol Chem. 273:30057–30060. 1998. View Article : Google Scholar : PubMed/NCBI
25	Farmer SR: Transcriptional control of adipocyte formation. Cell Metab. 4:263–273. 2006. View Article : Google Scholar : PubMed/NCBI
26	Shimano H: Sterol regulatory element-binding protein family as global regulators of lipid synthetic genes in energy metabolism. Vitam Horm. 65:167–194. 2002. View Article : Google Scholar : PubMed/NCBI
27	Palmer DG, Rutter GA and Tavare JM: Insulin-stimulated fatty acid synthase gene expression does not require increased sterol response element binding protein 1 transcription in primary adipocytes. Biochem Biophys Res Commun. 291:439–443. 2002. View Article : Google Scholar : PubMed/NCBI
28	Yeaman SJ, Smith GM, Jepson CA, Wood SL and Emmison N: The multifunctional role of hormone-sensitive lipase in lipid metabolism. Adv Enzyme Regul. 34:355–370. 1994. View Article : Google Scholar : PubMed/NCBI
29	Kim MS, Wang Y and Rodrigues B: Lipoprotein lipase mediated fatty acid delivery and its impact in diabetic cardiomyopathy. Biochim Biophys Acta. 1821:800–808. 2012. View Article : Google Scholar
30	Gonzales AM and Orlando RA: Role of adipocyte-derived lipoprotein lipase in adipocyte hypertrophy. Nutr Metab (Lond). 4:222007. View Article : Google Scholar