WNT/ß-catenin pathway mediates the anti-adipogenic effect of platycodin D, a natural compound found in Platycodon grandiflorum.

ABSTRACT

AIMS: This study was conducted to suggest the role of WNT/ß-catenin pathway in the anti-adipogenic effect of platycodin D, a natural compound found in Platycodon grandiflorum. MAIN METHODS: Gene knockdown experiments using small interfering RNA (siRNA) transfection were conducted to elucidate crucial role of ß-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/ß-catenin pathway. KEY FINDINGS: During the adipocyte differentiation of 3 T3-L1 cells, members of the WNT/ß-catenin pathway were normally down-regulated, whereas platycodin D significantly reinstated the WNT/ß-catenin pathway. The mRNA and protein expressions of disheveled (DVL) 2, which stabilize ß-catenin, were increased by platycodin D treatment, but the protein level of AXIN, which induces the degradation of ß-catenin, was decreased in platycodin D-treated cells. The nuclear level of ß-catenin was normally down-regulated during adipogenesis, but platycodin D treatment led to the accumulation of ß-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 ß-catenin siRNA-transfected cells compared with those of control siRNA-transfected cells. ß-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. SIGNIFICANCE: WNT/ß-catenin pathway can be used as a therapeutic target of natural compounds for the regulation of adipogenesis.