Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Acer okamotoanum Nakai Leaf Extract Inhibits Adipogenesis Via Suppressing Expression of PPAR γ and C/EBP α in 3T3-L1 Cells

  • Kim, Eun-Joo (Department of Microbiology, College of Natural Sciences, Pukyong National University) ;
  • Kang, Min-jae (Department of Microbiology, College of Natural Sciences, Pukyong National University) ;
  • Seo, Yong Bae (Department of Microbiology, College of Natural Sciences, Pukyong National University) ;
  • Nam, Soo-Wan (Biomedical Engineering and Biotechnology Major, Division of Applied Bioengineering, College of Engineering, Dong-Eui University) ;
  • Kim, Gun-Do (Department of Microbiology, College of Natural Sciences, Pukyong National University)
  • Received : 2018.02.01
  • Accepted : 2018.08.07
  • Published : 2018.10.28
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Abstract

The genus Acer contains several species with various bioactivities including antioxidant, antitumor and anti-inflammatory properties. However, Acer okamotoanum Nakai, one species within this genus has not been fully studied yet. Therefore, in this study, we investigated the anti-adipogenic activities of leaf extract from A. okamotoanum Nakai (LEAO) on 3T3-L1 preadipocytes. Adipogenesis is one of the cell differentiation processes, which converts preadipocytes into mature adipocytes. Nowadays, inhibition of adipogenesis is considered as an effective strategy in the field of anti-obesity research. In this study, we observed that LEAO decreased the accumulation of lipid droplets during adipogenesis and down-regulated the expression of key adipogenic transcription factors such as peroxisome proliferator-activated receptor ${\gamma}$ (PPAR ${\gamma}$) and CCAAT/enhancer binding protein ${\alpha}$ (C/EBP ${\alpha}$). In addition, LEAO inactivated PI3K/Akt signaling and its downstream factors that promote adipogenesis by inducing the expression of PPAR ${\gamma}$. LEAO also activated ${\beta}$-catenin signaling, which prevents the adipogenic program by suppressing the expression of PPAR ${\gamma}$. Therefore, we found that treatment with LEAO is effective for attenuating adipogenesis in 3T3-L1 cells. Consequently, these findings suggest that LEAO has the potential to be used as a therapeutic agent for preventing obesity.

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References

  1. Pi-Sunyer FX. 2002. The obesity epidemic: pathophysiology and consequences of obesity. Obesity 10: 97S-104S. https://doi.org/10.1038/oby.2002.202
  2. Lawrence VJ, Kopelman PG. 2004. Medical consequences of obesity. Clin. Dermatol. 22: 296-302. https://doi.org/10.1016/j.clindermatol.2004.01.012
  3. Marti A, Moreno-Aliaga M, Hebebrand J, Martinez J. 2004. Genes, lifestyles and obesity. Int. J. Obes. 28: S29-S36.
  4. Spiegelman BM, Flier JS. 1996. Adipogenesis and obesity: rounding out the big picture. Cell 87: 377-389. https://doi.org/10.1016/S0092-8674(00)81359-8
  5. Ali AT, Hochfeld WE, Myburgh R, Pepper MS. 2013. Adipocyte and adipogenesis. Eur. J. Cell Biol. 92: 229-236. https://doi.org/10.1016/j.ejcb.2013.06.001
  6. Farmer SR. 2006. Transcriptional control of adipocyte formation. Cell Metabolism. 4: 263-273. https://doi.org/10.1016/j.cmet.2006.07.001
  7. Rosen ED, MacDougald OA. 2006. Adipocyte differentiation from the inside out. Nature Reviews. Mol. Cell Biol. 7: 885-896.
  8. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, et al. 1999. $PPAR{\gamma}$ is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 4: 611-617. https://doi.org/10.1016/S1097-2765(00)80211-7
  9. Saltiel AR, Kahn CR. 2001. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414: 799-806. https://doi.org/10.1038/414799a
  10. Laplante M, Sabatini DM. 2012. mTOR signaling in growth control and disease. Cell 149: 274-293. https://doi.org/10.1016/j.cell.2012.03.017
  11. Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A. 2009. Adipogenesis and WNT signalling. Trends Endocrinol. Metab. 20: 16-24. https://doi.org/10.1016/j.tem.2008.09.002
  12. Bi W, Gao Y, S hen J, He C, Liu H, Peng Y, et al. 2016. Traditional uses, phytochemistry, and pharmacology of the genus Acer (maple): a review. J. Ethnopharmacol. 189: 31-60. https://doi.org/10.1016/j.jep.2016.04.021
  13. Jin L, Han JG, Ha JH, Jeong HS, Kwon MC, Jeong MH, et al. 2008. Comparison of antioxidant and glutathione S-transferase activities of extracts from Acer mono and A. okamotoanum. Korean J. Med. Crop Sci. 16: 427-433.
  14. Yang H, Hwang I, Koo TH, Ahn HJ, Kim S, Park MJ, et al. 2012. Beneficial effects of Acer okamotoanum sap on ${\small{L}}$-NAME-induced hypertension-like symptoms in a rat model. Mol. Med. Rep. 5: 427-431.
  15. Yoo Y, Jung E, Kang H, Choi I, Choi K, Jeung E. 2011. The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats. Int. J. Mol. Med. 28: 489-495.
  16. Rayalam S, Della-Fera MA, Baile CA. 2008. Phytochemicals and regulation of the adipocyte life cycle. J. Nutr. Biochem. 19: 717-726. https://doi.org/10.1016/j.jnutbio.2007.12.007
  17. Yun JW. 2010. Possible anti-obesity therapeutics from nature-a review. Phytochemistry 71: 1625-1641. https://doi.org/10.1016/j.phytochem.2010.07.011
  18. Feng S, Reuss L, Wang Y. 2016. Potential of natural products in the inhibition of adipogenesis through regulation of $PPAR{\gamma}$ expression and/or its transcriptional activity. Molecules 21: 1278. https://doi.org/10.3390/molecules21101278
  19. Farmer S. 2005. Regulation of PPAR [gamma] activity during adipogenesis. Int. J. Obes. 29: S13-S16. https://doi.org/10.1038/sj.ijo.0802907
  20. Rosen ED, Hsu CH, Wang X, S akai S , Freeman MW, Gonzalez FJ, et al. 2002. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev. 16: 22-26. https://doi.org/10.1101/gad.948702
  21. Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F. 2004. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 86: 839-848. https://doi.org/10.1016/j.biochi.2004.09.018
  22. Kim JB, Spiegelman BM. 1996. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 10: 1096-1107. https://doi.org/10.1101/gad.10.9.1096
  23. Chirala SS , Wakil SJ. 2004. Structure and function of animal fatty acid synthase. Lipids 39: 1045-1053. https://doi.org/10.1007/s11745-004-1329-9
  24. Fu Y, Luo N, Klein RL, Garvey WT. 2005. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J. Lipid Res. 46: 1369-1379. https://doi.org/10.1194/jlr.M400373-JLR200
  25. Whitehead JP, Clark S F, Urso B, James DE. 2000. Signalling through the insulin receptor. Curr. Opin. Cell Biol. 12: 222-228. https://doi.org/10.1016/S0955-0674(99)00079-4
  26. Khan A, Pessin J. 2002. Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways. Diabetologia 45: 1475-1483. https://doi.org/10.1007/s00125-002-0974-7
  27. Sasaki T, Takasuga S, Sasaki J, Kofuji S, Eguchi S, Yamazaki M, et al. 2009. Mammalian phosphoinositide kinases and phosphatases. Prog. Lipid Res. 48: 307-343. https://doi.org/10.1016/j.plipres.2009.06.001
  28. Zhang HH, Huang J, Duvel K, Boback B, Wu S , Squillace RM, et al. 2009. Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway. PLoS One 4: e6189. https://doi.org/10.1371/journal.pone.0006189
  29. Kim JE, Chen J. 2004. Regulation of peroxisome proliferator-activated receptor-gamma activity by mammalian target of rapamycin and amino acids in adipogenesis. Diabetes 53: 2748-2756. https://doi.org/10.2337/diabetes.53.11.2748
  30. Laplante M, Sabatini DM. 2009. An emerging role of mTOR in lipid biosynthesis. Curr. Biol. 19: R1046-R1052. https://doi.org/10.1016/j.cub.2009.09.058
  31. Fox HL, Kimball SR, Jefferson LS, Lynch CJ. 1998. Amino acids stimulate phosphorylation of p70S6k and organization of rat adipocytes into multicellular clusters. Am. J. Physiol. 274: C206-C213. https://doi.org/10.1152/ajpcell.1998.274.1.C206
  32. Wu D, Pan W. 2010. GSK3: a multifaceted kinase in Wnt signaling. Trends Biochem. Sci. 35: 161-168. https://doi.org/10.1016/j.tibs.2009.10.002
  33. Taurin S, Sandbo N, Qin Y, Browning D, Dulin NO. 2006. Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase. J. Biol. Chem. 281: 9971-9976. https://doi.org/10.1074/jbc.M508778200
  34. Grimes CA, Jope RS. 2001. The multifaceted roles of glycogen synthase kinase $3{\beta}$ in cellular signaling. Prog. Neurobiol. 65: 391-426. https://doi.org/10.1016/S0301-0082(01)00011-9
  35. Ding VW, Chen RH, McCormick F. 2000. Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling. J. Biol. Chem. 275: 32475-32481. https://doi.org/10.1074/jbc.M005342200
  36. Fang D, Hawke D, Zheng Y, Xia Y, Meisenhelder J, Nika H, et al. 2007. Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. J. Biol. Chem. 282: 11221-11229. https://doi.org/10.1074/jbc.M611871200
  37. Liu J, Farmer SR. 2004. Regulating the balance between peroxisome proliferator-activated receptor gamma and beta-catenin signaling during adipogenesis. A glycogen synthase kinase 3beta phosphorylation-defective mutant of beta-catenin inhibits expression of a subset of adipogenic genes. J. Biol. Chem. 279: 45020-45027. https://doi.org/10.1074/jbc.M407050200

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