title: Phytoestrogenic molecule desmethylicaritin suppressed adipogenesis via Wnt/β-catenin signaling pathway.
abstract: Epimedium flavonoids inhibit extravascular lipid deposition during prevention of steroid-associated osteonecrosis. Desmethylicaritin is a bioactive metabolite of Epimedium flavonoids in serum. As it is well known that estrogen inhibits aidpogenesis, so we hypothesized that desmethylicaritin as a phytoestrogen might have the potential to inhibit lipid deposition. This study was designed to investigate the effect of desmethylicaritin on adipogenesis and its underlying mechanism in vitro. Adipogenesis was assessed by Oil Red O staining in 3T3-L1 preadipocytes. Bromodeoxyuridine was used to test the clonal expansion. Further, the mRNA level and protein expression of adipgenic and related factors were detected by qRT-PCR and western blot, respectively. The nuclear location of β-catenin was identified using immunofluoresence assay. Our results showed that desmethylicaritin suppressed the adipogenesis in 3T3-L1 cells in a dose-dependent manner. In addition, desmethylicaritin inhibited clonal expansion during adipogenesis. Desmethylicaritin did not affect CCAAT/enhancer binding protein δ and β mRNA expression, but decreased the mRNA expression of CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, adipocyte lipid-binding protein and lipoprotein lipase. Desmethylicaritin up-regulated the mRNA expression of Wnt10b that was however down-regulated after adipogenic induction. Desmethylicaritin increased the protein expression of β-catenin both in the cytoplasm and nuclei and immunofluorescence results confirmed that desmethylicaritin increased nuclear translocation of β-catenin. Above findings implied that desmethylicaritin was able to inhibit adipogenesis and Wnt/β-catenin signaling pathway was regulated by desmethylicaritin in the process of suppression of adipogenesis. Above findings supported desmethylicaritin as a novel phytochemical agent for potential prevention of disorders involving lipid metabolism.
authors.affiliation: Translational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Xin-Luan
authors.initials: XL
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Zheng
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Xie
authors.forename: Dong
authors.initials: D
authors.lastname: Yao
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Liu
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Yao
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Yao
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D034181:Epimedium / Q000737:chemistry; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000235:genetics; D051379:Mice; D048789:Phytoestrogens / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005419:Flavonoids; D048789:Phytoestrogens; D051153:Wnt Proteins; D051176:beta Catenin; C499404:desmethylicaritin; D008071:Lipoprotein Lipase
keywords: Adipogenesis; Desmethylicaritin; PPARγ; Wnt/β-catenin