WNT/beta-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/beta-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 beta-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/beta-catenin pathway. Key findings: During the adipocyte differentiation of 313-L1 cells, members of the WNT/beta-catenin pathway were normally down-regulated, whereas platycodin D significantly reinstated the WNT/beta-catenin pathway. The mRNA and protein expressions of disheveled (DVL) 2, which stabilize beta-catenin, were increased by platycodin D treatment, but the protein level of AXIN, which induces the degradation of beta-catenin, was decreased in platycodin D-treated cells. The nuclear level of beta-catenin was normally down-regulated during adipogenesis, but platycodin D treatment led to the accumulation of beta-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)gamma. The anti-adipogenic effects of platycodin D were significantly attenuated in beta-catenin siRNA-transfected cells compared with those of control siRNA-transfected cells. beta-catenin siRNA transfection significantly recovered the levels of PPAR gamma. CCAAT/enhancer binding protein (C/EBP)alpha 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/beta-catenin pathway can be used as a therapeutic target of natural compounds for the regulation of adipogenesis. (C) 2011 Elsevier Inc. All rights reserved.