title: Shikonin inhibits adipogenesis by modulation of the WNT/β-catenin pathway.
abstract: OBJECTIVE
  Our previous study showed for the first time that shikonin, a natural compound isolated from Lithospermun erythrorhizon Sieb. Et Zucc, inhibits adipogenesis and fat accumulation. This study was conducted to investigate the molecular mechanism of the anti-adipogenic effects of shikonin.
  
  
  METHODS
  Gene knockdown experiments using small interfering RNA (siRNA) transfection were conducted to elucidate the crucial role of β-catenin in the anti-adipogenic effects of shikonin.
  
  
  RESULTS
  Shikonin prevented the down-regulation of β-catenin and increased the level of its transcriptional product, cyclin D1, during adipogenesis of 3T3-L1 cells, preadipocytes originally derived from mouse embryo. β-catenin was a crucial mediator of the anti-adipogenic effects of shikonin, as determined by siRNA-mediated knockdown. Shikonin-induced reductions of the major transcription factors of adipogenesis including peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α, and lipid metabolizing enzymes including fatty acid binding protein 4 and lipoprotein lipase, as well as intracellular fat accumulation, were all significantly recovered by siRNA-mediated knockdown of β-catenin. Among the genes located in the WNT/β-catenin pathway, the levels of WNT10B and DVL2 were significantly up-regulated, whereas the level of AXIN was down-regulated by shikonin treatment.
  
  
  CONCLUSIONS
  This study clearly shows that shikonin inhibits adipogenesis by the modulation of WNT/β-catenin pathway in vitro, and also suggests that WNT/β-catenin pathway can be used as a therapeutic target for obesity and related diseases using a natural compound like shikonin, even though the in vivo effects of shikonin and its clinical significance remain to be elucidated.
authors.affiliation: Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Korea.
authors.forename: Haeyong
authors.initials: H
authors.lastname: Lee
authors.forename: Sungmin
authors.initials: S
authors.lastname: Bae
authors.forename: Kijeong
authors.initials: K
authors.lastname: Kim
authors.forename: Wonyong
authors.initials: W
authors.lastname: Kim
authors.forename: Sang-In
authors.initials: SI
authors.lastname: Chung
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.forename: Yoosik
authors.initials: Y
authors.lastname: Yoon
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors; D051176:beta Catenin / Q000037:antagonists & inhibitors*
chemical_list: D009285:Naphthoquinones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; C016101:shikonin