DOI QR코드

DOI QR Code

Inhibitory Effects of (-)-Epigallocatechin-3-gallate on Adipogenesis via AMPK Activation in 3T3-L1 Cells

AMPK 활성화를 통한 (-)-Epigallocatechin-3-gallate의 지방세포분화 억제 효과

  • Kim, Younghwa (School of Food Biotechnology and Nutrition, Kyungsung University)
  • 김영화 (경성대학교 식품응용공학부)
  • Received : 2017.07.27
  • Accepted : 2017.09.12
  • Published : 2017.10.31

Abstract

(-)-Epigallocatechin-3-gallate (EGCG) is a major catechin found in green tea. It is reported that EGCG possesses various health benefits including anti-cancer, antioxidant, anti-diabetes, and anti-obesity. The objective of this study was to investigate the effects of EGCG on adipogenesis via activation of AMP-activated protein kinase (AMPK) pathway in 3T3-L1 preadipocytes. In order to determine the effects of EGCG on adipogenesis, preadipocyte differentiation was induced in the presence or absence of EGCG ($0{\sim}100{\mu}M$) for a period of 6 days. EGCG significantly inhibited fat accumulation and suppressed the expression of adipogenic specific proteins including peroxisome proliferator-activated receptor (PPAR)-${\gamma}$. Also, EGCG markedly increased the activation of AMPK and acetyl-CoA carboxylase (ACC) and the production of intracellular reactive oxygen species (ROS). However, any pretreatment with a specific AMPK inhibitor, compound C, abolished the inhibitory effects of the EGCG on $PPAR{\gamma}$ expression. This study suggests that EGCG has anti-adipogenic effects through modulation of the AMPK signaling pathway and therefore, may be a promising antiobesity agent.

Keywords

References

  1. Ahmad N, Mukhtar H. 1999. Green tea polyphenols and cancer: biologic mechanisms and practical implications. Nutr Rev 57:78-83
  2. Assifi MM, Suchankova G, Constant S, Prentki S, Saha AK, Ruderman NB. 2005. AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved/carbohydrate-refed rats. Am J Physiol Endoc M 289:E794-800 https://doi.org/10.1152/ajpcell.00632.2004
  3. Carling D, Mayer FV, Sanders MJ, Gamblin SJ. 2011. AMPactivated protein kinase: Nature’s energy sensor. Nat Chem Biol 7:512-518 https://doi.org/10.1038/nchembio.610
  4. Chan CY, Wei L, Castro-Munozledo F, Koo WL. 2011. (-)-Epigallocatechin-3-gallate blocks 3T3-L1 adipose conversion by inhibition of cell proliferation and suppression of adipose phenotype expression. Life Sci 89:779-785 https://doi.org/10.1016/j.lfs.2011.09.006
  5. Choi JH, Park YH, Lee IS, Lee SP, Yu MH. 2013. Antioxidant activity and inhibitory effect of Aster scaber Thunb. extract on adipocyte differentiation in 3T3-L1 cells. Korean J Food Sci Technol 45:356-363 https://doi.org/10.9721/KJFST.2013.45.3.356
  6. Choi Y, Kim Y, Ham H, Park Y, Jeong HS, Lee J. 2011. Nobiletin suppresses adipogenesis by regulating the expression of adipogenic transcription factors and the activation of AMP-activated protein kinase (AMPK). J Agric Food Chem 59:12843-12849 https://doi.org/10.1021/jf2033208
  7. Darlington GJ, Ross SE, MacDougald OA. 1998. The role of C/EBP genes in adipocyte differentiation. J Giol Chem 273: 30057-30060
  8. Daval M, Foufelle F, Ferre, P. 2006. Functions of AMP-activated protein kinase in adipose tissue. J Physiol 574:55-62 https://doi.org/10.1113/jphysiol.2006.111484
  9. Foretz MD, Carling D, Guichard C, Ferre P, Foufelle F. 1998. AMP-activated protein kinase inhibits the glucose activited expression of fatty acid synthase gene in rat hepatocytes. J Biol Chem 273:14767-14771 https://doi.org/10.1074/jbc.273.24.14767
  10. Graham HN. 1992. Green tea composition, consumption, and polyphenol chemistry. Prev Med 21:334-350 https://doi.org/10.1016/0091-7435(92)90041-F
  11. Habinowski SA, Witters LA. 2001. The effects of AICAR on adipocyte differentiation of 3T3-L1 cells. Biochem Biophys Res Commun 286:852-856 https://doi.org/10.1006/bbrc.2001.5484
  12. Han Y, Wang Q, Song P, Zhu Y, Zou MH. 2010. Redox regulation of the AMP-activated protein kinase. PLoS ONE 5: e15420 https://doi.org/10.1371/journal.pone.0015420
  13. Hardie DG. 2003. The AMP-activated protein kinase cascade: The key sensor of cellular energy status. Endocrinology 144: 5179-5183 https://doi.org/10.1210/en.2003-0982
  14. Hwang JT, Ha J, Park IJ, Lee SK, Baik HW, Kim YM. 2007. Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway. Cancer Lett 247:115-121 https://doi.org/10.1016/j.canlet.2006.03.030
  15. Hwang JT, Park IJ, Shin JI, Lee YK, Lee SK, Baik HW, Ha J, Park OJ. 2005. Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP activated protein kinase. Biochem Biophys Res Commun 338:694-699 https://doi.org/10.1016/j.bbrc.2005.09.195
  16. Kao YH, Hiipakka RA, Liao S. 2000. Modulation of endocrine systems and food intake by green tea epigallocatechin gallate. Endocrinology 141:980-987 https://doi.org/10.1210/endo.141.3.7368
  17. Kim JD, Lee BI, Jeon YH, Bak JP, Jin HL, Lim BO. 2010. Anti-oxidative and anti-inflammatory effects of green tea mixture and dietary fiber on liver of high fat diet-induced obese rats. Korean J Med Crop Sci 18:224-230
  18. Kim Y, Lee J. 2015. Esculetin, a coumarin derivative, suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes. J Funct Foods 12:509-515 https://doi.org/10.1016/j.jff.2014.12.004
  19. Kim Y, Lee J. 2016. Effect of (-)-epigallocatechin-3-gallate on anti-inflammatory response via heme oxygenase-1 induction during adipocyte-macrophage interactions. Food Sci Biotechnol 25:1767-1773 https://doi.org/10.1007/s10068-016-0269-2
  20. Lee WJ, Koh EH, Won JC, Kim MS, Park JY, Lee KU. 2005. Obesity: The role of hypothalamic AMP-activated protein kinase in body weight regulation. Int J Biochem Cell Biol 37:2254-2259 https://doi.org/10.1016/j.biocel.2005.06.019
  21. Lin J, Della-Fera MA, Baile CA. 2005. Green tea polyphenol epigallocatechin gallate inhibits adipogenesis and induces apoptosis in 3T3-L1 adipocytes. Obes Res 13:982-990 https://doi.org/10.1038/oby.2005.115
  22. Liu HS, Chen YH, Hung PF, Kao YH. 2006. Inhibitory effect of green tea (-)-epigallocatechin gallate on resistin gene expression in 3T3-L1 adipocytes depends on the ERK pathway. Am J Physiol. Endoc M 290:E273-E281
  23. Moon HS, Chung CS, Lee HG, Kim TG, Choi YJ, Cho CS. 2007. Inhibitory effect of (-)-epigallocatechin-3-gallate on lipid accumulation of 3T3-L1 cells. Obesity 15:2571-2582 https://doi.org/10.1038/oby.2007.309
  24. Nagao T, Komine Y, Soga S, Meguro S, Hase T, Tanaka Y, Tokimitsu I. 2005. Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men. Am J Clin Nutr 81:122-129 https://doi.org/10.1093/ajcn/81.1.122
  25. Oakley FD, Abbott D, Li Q, Engelhardt JF. 2009. Signaling components of redox active endosomes: The redoxosomes. Antioxid Redox Signal 11:1313-1333 https://doi.org/10.1089/ars.2008.2363
  26. Park YB, Lim JH, Seo EW. 2015. Anti-obesity effect of byproduct from soybean on mouse fed a hig fat diet. Korean J Plant Res 28:168-177 https://doi.org/10.7732/kjpr.2015.28.2.168
  27. Rosen ED, Hsu CH, Wang S, Sakai X, Freeman MW, Gonzalez FJ, Spiegelman BM. 2002. $C/EBP{\alpha}$ induces adipogenesis through PPAR: a unified pathway. Genes Dev 16:22-26 https://doi.org/10.1101/gad.948702
  28. Sullivan JE, Brocklehurst KJ, Marley AE, Carey F, Carling D, Beri RK. 1994. Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett 353:33-36 https://doi.org/10.1016/0014-5793(94)01006-4
  29. 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
  30. Wang H, Joseph JA. 1999. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27:612-616 https://doi.org/10.1016/S0891-5849(99)00107-0
  31. White UA, Stephens JM. 2010. Transcriptional factors that promote formation of white adipose tissue. Mol Cell Endocrinol 318:10-14 https://doi.org/10.1016/j.mce.2009.08.023

Cited by

  1. Comparative Study of the Effects of Light Controlled Germination Conditions on Saponarin Content in Barley Sprouts and Lipid Accumulation Suppression in HepG2 Hepatocyte and 3T3-L1 Adipocyte Cells Usi vol.25, pp.22, 2020, https://doi.org/10.3390/molecules25225349