title: WNT/β-catenin pathway mediates the anti-adipogenic effect of platycodin D, a natural compound found in Platycodon grandiflorum.
abstract: OBJECTIVE
  This study was conducted to suggest the role of WNT/β-catenin pathway in the anti-adipogenic effect of platycodin D, a natural compound found in Platycodon grandiflorum.
  
  
  METHODS
  Gene knockdown experiments using small interfering RNA (siRNA) transfection were conducted to elucidate crucial role of β-catenin in the anti-adipogenic effects of platycodin D. Real-Time PCR and Western blot were used to analyze the expression levels of mRNAs and proteins in the WNT/β-catenin pathway.
  
  
  RESULTS
  During the adipocyte differentiation of 3 T3-L1 cells, members of the WNT/β-catenin pathway were normally down-regulated, whereas platycodin D significantly reinstated the WNT/β-catenin pathway. The mRNA and protein expressions of disheveled (DVL) 2, which stabilize β-catenin, were increased by platycodin D treatment, but the protein level of AXIN, which induces the degradation of β-catenin, was decreased in platycodin D-treated cells. The nuclear level of β-catenin was normally down-regulated during adipogenesis, but platycodin D treatment led to the accumulation of β-catenin in the nucleus which resulted in the up-regulation of its target genes, cyclin D (CCND) 1 and peroxisome proliferator-activated receptor gamma (PPAR)γ. The anti-adipogenic effects of platycodin D were significantly attenuated in β-catenin siRNA-transfected cells compared with those of control siRNA-transfected cells. β-catenin siRNA transfection significantly recovered the levels of PPARγ, CCAAT/enhancer binding protein (C/EBP)α and fatty acid binding protein (FABP)4 as well as intracellular lipid droplet formation, all of which were reduced by platycodin D treatment.
  
  
  CONCLUSIONS
  WNT/β-catenin pathway can be used as a therapeutic target of natural compounds for the regulation of adipogenesis.
authors.affiliation: Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
authors.forename: Haeyong
authors.initials: H
authors.lastname: Lee
authors.forename: Sungmin
authors.initials: S
authors.lastname: Bae
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Yoosik
authors.initials: Y
authors.lastname: Yoon
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D018929:Cell Culture Techniques; D051379:Mice; D008517:Phytotherapy; D018517:Plant Roots; D031238:Platycodon / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000032:analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014162:Transfection; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D012503:Saponins; D014315:Triterpenes; D051153:Wnt Proteins; D051176:beta Catenin; D012313:RNA; C108953:platycodin D