Anti-Adipogenic Activity of Ailanthoidol on 3T3-L1 Adipocytes

  • Park, Ju-Hyung (Department of Biomedical Science, Catholic University of Daegu) ;
  • Jun, Jong-Gab (Department of Chemistry and Institute of Natural Medicine, Hallym University) ;
  • Kim, Jin-Kyung (Department of Biomedical Science, Catholic University of Daegu)
  • 투고 : 2014.03.25
  • 심사 : 2014.05.24
  • 발행 : 2014.06.30

초록

Previous our study demonstrated that ailanthoidol (3-deformylated 2-arylbenzo[b]furan), a neolignan from Zanthoxylum ailanthoides or Salvia miltiorrhiza Bunge, is a novel anti-inflammatory agent. In this investigation, we examined the anti-adipogenic effect of ailanthoidol. Our data showed that ailanthoidol suppressed lipid droplet formation and adipocyte differentiation in 3T3-L1 cells. Treatment of the 3T3-L1 adipocytes with ailanthoidol resulted in an attenuation of the releases of leptin and interleukin-6. The expression of peroxisome proliferator-activated receptor $(PPAR){\gamma}$ and CCAAT/enhancer-binding protein $(C/EBP){\alpha}$, the central transcriptional regulators of adipogenesis, was decreased by treatment with ailanthoidol. Additionally, ailanthoidol treatment increased the phosphorylation levels of 5' adenosine monophosphate-activated protein kinase. These results suggest that ailanthoidol effectively suppresses adipogenesis and that it exerts its role mainly through the significant down-regulation of $PPAR{\gamma}$ and $C/EBP{\alpha}$ expression. Our findings provide important insights into the mechanisms underlying the anti-adipogenic activity of ailanthoidol.

키워드

참고문헌

  1. Carling D. The AMP-activated protein kinase cascade-a unifying system for energy control. Trends Biochem Sci. 2004. 29: 18-24. https://doi.org/10.1016/j.tibs.2003.11.005
  2. Chavey C, Mari B, Monthouel MN, Bonnafous S, Anglard P, Van Obberghen E, Tartare-Deckert S. Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. J Biol Chem. 2003. 278: 11888-11896. https://doi.org/10.1074/jbc.M209196200
  3. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab. 2006. 4: 263-273. https://doi.org/10.1016/j.cmet.2006.07.001
  4. Green A, Rumberger JM, Stuart CA, Ruhoff MS. Stimulation of lipolysis by tumor necrosis factor-alpha in 3T3-L1 adipocytes is glucose dependent: implications for long-term regulation of lipolysis. Diabetes. 2004. 53: 74-81. https://doi.org/10.2337/diabetes.53.1.74
  5. Hardie DG. AMPK: a key regulator of energy balance in the single cell and the whole organism. Int J Obes. 2008. 32: S7-12. https://doi.org/10.1038/ijo.2008.116
  6. Hsu CL, Yen GC. Phenolic compounds: evidence for inhibitory effects against obesity and their underlying molecular signaling mechanisms. Mol Nutr Food Res. 2008. 52: 53-61. https://doi.org/10.1002/mnfr.200700393
  7. 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: 17-22. https://doi.org/10.1016/j.nbt.2009.03.005
  8. Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005. 1: 15-25. https://doi.org/10.1016/j.cmet.2004.12.003
  9. Kim JK, Jun JG. Ailanthoidol suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice. J Cell Biochem. 2011. 112: 3816-3823. https://doi.org/10.1002/jcb.23312
  10. Lee EJ, Kang M, Kim YS. Platycodin D inhibits lipogenesis through AMPK${\alpha}$-PPAR${\gamma}$2 in 3T3-L1 cells and modulates fat accumulation in obese mice. Planta Med. 2012. 78: 1536-1542. https://doi.org/10.1055/s-0032-1315147
  11. Lee YJ, Kao ES, Chu CY, Lin WL, Chiou YH, Tseng TH. Inhibitory effect of ailanthoidol on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mouse skin. Oncol Rep. 2006. 16: 921-927.
  12. Li MF, Cheung BM. Rise and fall of anti-obesity drugs. World J Diabetes. 2011. 2: 19-23. https://doi.org/10.4239/wjd.v2.i2.19
  13. Otto TC, Lane MD. Adipose development: from stem cell to adipocyte. Crit Rev Biochem Mol Biol. 2005. 40: 229-242. https://doi.org/10.1080/10409230591008189
  14. Poulos SP, Dodson MV, Hausman GJ. Cell line models for differentiation: preadipocytes and adipocytes. Exp Biol Med. 2010. 235: 1185-1193. https://doi.org/10.1258/ebm.2010.010063
  15. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001. 286: 327-334. https://doi.org/10.1001/jama.286.3.327
  16. Purohit A, Ghilchik MW, Duncan L, Wang DY, Singh A, Walker MM, Reed MJ. Aromatase activity and interleukin-6 production by normal and malignant breast tissues. J Clin Endocrinol Metab. 1995. 80: 3052-3058.
  17. Rhyu J, Kim MS, You MK, Bang MA, Kim HA. Pear pomace water extract inhibits adipogenesis and induces apoptosis in 3T3-L1 adipocytes. Nutr Res Pract. 2014. 8: 33-39 https://doi.org/10.4162/nrp.2014.8.1.33
  18. Rosen ED Spiegelman BM. Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol. 2000. 16: 145-171. https://doi.org/10.1146/annurev.cellbio.16.1.145
  19. Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, Spiegelman BM. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev. 2002. 16: 22-26. https://doi.org/10.1101/gad.948702
  20. Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 2006. 7: 885-896. https://doi.org/10.1038/nrm2066
  21. Rossmeisl M, Flachs P, Brauner P, Sponarova J, Matejkova O, Prazak T, Ruzickova J, Bardova K, Kuda O, Kopecky, J. Role of energy charge and AMP-activated protein kinase in adipocytes in the control of body fat stores. Int J Obes Relat Metab Disord. 2004. 28: S38-44.
  22. Spiegelman BM, Choy L, Hotamisligil GS, Graves RA, Tontonoz P. Regulation of adipocyte gene expression in differentiation and syndroms of obesity/diabetes. J Biol Chem. 1993. 268: 6823-2866.
  23. Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006. 6: 772-783. https://doi.org/10.1038/nri1937
  24. Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM. mPPARgamma2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994. 8: 1224-1234. https://doi.org/10.1101/gad.8.10.1224
  25. Vermaak I, Viljoen AM, Hamman JH. Natural products in antiobesity therapy. Nat Prod Rep. 2011. 28: 1493-1533. https://doi.org/10.1039/c1np00035g
  26. White UA, Stephens JM. Neuropoietin activates STAT3 independent of LIFR activation in adipocytes. Biochem Biophys Res Commun. 2010. 395: 48-50. https://doi.org/10.1016/j.bbrc.2010.03.132
  27. World Health Organisation. Global status report on noncommunicable diseases 2010. Chapter 1. Burden: mortality, morbidity and risk factors. World Health Organization. 2011. 9-31.