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Anti-Obesity Effect of Ethyl Acetate Extracts from Agrimonia pilosa Ledeb. in 3T3-L1 Preadipocytes

3T3-L1 지방전구세포에서 용아초 에틸아세테이트 추출물의 항비만 효과

  • Lee, Jung-A (Natural Products Research Institute, Gyeonggi Institute of Science & Technology Promotion) ;
  • Ahn, Eun-Kyung (Natural Products Research Institute, Gyeonggi Institute of Science & Technology Promotion) ;
  • Hong, Seong-Su (Natural Products Research Institute, Gyeonggi Institute of Science & Technology Promotion) ;
  • Oh, Joa-Sub (Natural Products Research Institute, Gyeonggi Institute of Science & Technology Promotion)
  • 이정아 ((재) 경기과학기술진흥원 천연물신약연구소) ;
  • 안은경 ((재) 경기과학기술진흥원 천연물신약연구소) ;
  • 홍성수 ((재) 경기과학기술진흥원 천연물신약연구소) ;
  • 오좌섭 ((재) 경기과학기술진흥원 천연물신약연구소)
  • Received : 2011.10.11
  • Accepted : 2012.01.11
  • Published : 2012.02.29

Abstract

To evaluate the anti-obesity effect of Agrimonia pilosa L., this study investigated that ethyl acetate extract from A. pilosa L. (EAAP) suppresses lipid accumulation and inhibits expression of adipogenic marker genes, such as peroxisome proliferator activated receptor ${\gamma}$ (PPAR${\gamma}$), CCAAT-enhancer-binding protein ${\alpha}$ (C/EBP${\alpha}$), glucose transporter 4 (GLUT4), and adiponectin in 3T3-L1 preadipocytes. We demonstrated that EAAP inhibited adipocyte differentiation and expression of PPAR${\gamma}$ and C/EBP${\alpha}$ mRNA levels in a dose-dependent manner. In addition, EAAP reduced the PPAR${\gamma}$ transcriptional activity stimulated by rosiglitazone in HEK 293T cells and decreased the expression of GLUT4 and adiponectin in 3T3-L1 cells. These results suggest that EAAP inhibits preadipocyte differentiation and adipogenesis by blocking of PPAR${\gamma}$ and C/EBP${\alpha}$ gene expression in 3T3-L1 cells.

본 연구에서는 3T3-L1 지방전구세포를 이용하여 용아초 에틸아세테이트 추출물의 항비만 활성을 확인하고자 하였다. 용아초 에틸아세테이트 추출물에 의한 지방세포 분화 및 adipogenesis 저해 활성을 확인하기 위해 추출물을 3T3-L1 지방전구세포에 분화를 유도하면서 농도별(50, 100 ${\mu}g/mL$)로 처리하였고, 그 결과 용아초 에틸아세테이트 추출물은 지방세포의 분화를 억제시켰다. 이 같은 활성에 대한 기전을 확인하기 위해 PPAR${\gamma}$ 전사활성과 지방세포 분화에 관여하는 유전자들의 활성을 확인해 보았다. 실험 결과 용아초 에틸아세테이트 추출물은 PPAR${\gamma}$ 전사 활성을 억제시켰고 PPAR${\gamma}$ 및 C/EBP${\alpha}$의 mRNA 발현을 농도 의존적으로 감소시켰으며 지방세포 분화에 관여하는 adipokine들의 발현을 조절하는 것으로 나타났다. 따라서 용아초 에틸아세테이트 추출물의 항비만 효과는 지방 생성의 주요 전사인자인 PPAR${\gamma}$와 C/EBP${\alpha}$의 유전자 발현조절을 통해 지방 분화 억제 및 지방 축적을 효과적으로 감소시키는 것으로 보이며, 효과가 있는 농도가 100 ${\mu}g/mL$로 천연물질로써 비교적 낮은 농도에서 효과가 나타나는 것으로 보아 항비만 소재로의 개발 가능성이 있을 것으로 사료된다.

Keywords

References

  1. Visscher TL, Seidell JC. 2001. The public health impact of obesity. Annu Rev Public Health 22: 355-375. https://doi.org/10.1146/annurev.publhealth.22.1.355
  2. Darlington GJ, Ross SE, MacDougald OA. 1998. The role of C/EBP genes in adipocyte differentiation. J Biol Chem 273: 30057-30060. https://doi.org/10.1074/jbc.273.46.30057
  3. Rosen ED, Hsu CH, Wang X, Sakai X, Freeman MW, Gonzalez FJ, Spiegelman BM. 2001. C/EBP$\alpha$ induces adipogenesis through PPAR: a unified pathway. Genes Dev 16: 22-26. https://doi.org/10.1101/gad.948702
  4. Morrison RF, Farmer SR. 2000. Hormonal signaling and transcriptional control of adipocyte differentiation. J Nutr 130: 3116S-3121S. https://doi.org/10.1093/jn/130.12.3116S
  5. Rosen ED, Macdougald OA. 2006. Adipocyte differentiation from the in side out. Nat Rev Mol Cell Biol 7: 885-896. https://doi.org/10.1038/nrm2066
  6. An RB, Kim HC, Jeong GS, Oh SH, Oh H, Kim YC. 2005. Constituents of the aerial parts of Agrimonia pilosa. J Nat Prod 11: 196-199.
  7. Kato H, Li W, Koike M, Wang Y, Koike K. 2001. Phenolic glycosides from Agrimonia pilosa. Phytochemistry 71: 1925-1929. https://doi.org/10.1016/j.phytochem.2010.08.007
  8. Miyamoto K, Koshiura R, Ikeya Y, Taguchi H. 1985. Isolation of agrimoniin, an anritumour constituent, from the roots of Agrimonia pilosa Ledeb. Chem Pharm Bull 33: 3977-3982. https://doi.org/10.1248/cpb.33.3977
  9. Zhu L, Tan J, Wang B, He R, Liu Y, Zheng C. 2009. Antioxidant activities of aqueous extract from Agrimonia pilosa Ledeb and its fractions. Chem Biodivers 6: 1716-1726. https://doi.org/10.1002/cbdv.200800248
  10. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. 2000. Transcriptional regulation of adipogenesis. Genes & Dev 14: 1293-1307.
  11. Jeon T, Hwang SG, Hirai S, Matsui T, Yano H, Kawda T, Lim BU, Ki D. 2004. Red yeast rice extracts suppress adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 cells. Life Sci 75: 3195-3203. https://doi.org/10.1016/j.lfs.2004.06.012
  12. Cowherd RM, Lyle RE, McGehee Jr RE. 1999. Molecular regulation of adipocyte differentiation. Semin Cell Dev Biol 10: 3-10. https://doi.org/10.1006/scdb.1998.0276
  13. Cornelius P, MacDougald OA, Lane MD. 1994. Regulation of adipocyte development. Annu Rev Nutr 14: 99-129. https://doi.org/10.1146/annurev.nu.14.070194.000531
  14. MacDougald OA, Lane MD. 1995. Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem 64: 345-373. https://doi.org/10.1146/annurev.bi.64.070195.002021
  15. Ranganathan G, Unal R, Pokrovskaya I, Yao-Borengasser A, Phanavanh B, Lecka-Czernik B, Rasouli N, Kern PA. 2006. The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment. J Lipid Res 47: 2444-2449. https://doi.org/10.1194/jlr.M600248-JLR200
  16. Bogan JS, Mckee AE, Lodish HF. 2001. Insulin-responsive compartments containing GLUT4 in 3T3-L1 and CHO cells: regulation by amino acid concentrations. Mol Cell Biol 21: 4785-4806. https://doi.org/10.1128/MCB.21.14.4785-4806.2001
  17. Czech MP, Corvera S. 1999. Signaling mechanisms that regulate glucose transport. J Biol Chem 274: 1865-1868. https://doi.org/10.1074/jbc.274.4.1865
  18. Pessin JE, Thurmond DC, Elmendorf JS, Coker KJ, Okada S. 1999. Molecular basis of insulin-stimulated GLUT4 vesicle trafficking: location! location! location! J Biol Chem 274: 2593-2596. https://doi.org/10.1074/jbc.274.5.2593
  19. Shepherd PR, Kahn, BB. 1999. Glucose transporters and insulin action-implications for insulin resistance and diabetes mellitus. N Engl J Med 341: 248-257. https://doi.org/10.1056/NEJM199907223410406
  20. Kadowaki T, Yamauchi T. 2005. Adiponectin and adiponectin receptors. Endocr Rev 26: 439-451. https://doi.org/10.1210/er.2005-0005
  21. Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y. 2001. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50: 2094-2099. https://doi.org/10.2337/diabetes.50.9.2094

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