The WNT/ß-catenin pathway mediates the anti-adipogenic mechanism of SH21B, a traditional herbal medicine for the treatment of obesity.

ABSTRACT

AIM OF THE STUDY This study was conducted to elucidate the molecular mechanisms of SH21B, a traditional Korean herbal medicine commonly used for the treatment of obesity. MATERIALS AND METHODS: 3T3-L1 preadipocytes were differentiated into adipocytes in the presence or absence of SH21B. Changes in mRNA or protein levels were analyzed using microarray, real-time polymerase chain reaction and western blotting analyses. Small interference (si)RNA transfection experiments were conducted to elucidate the essential role of ß-catenin. RESULTS: Microarray analyses showed that components of the WNT/ß-catenin pathway including ß-catenin, cyclin D1 and dishevelled 2 were up-regulated more than two-fold as a result of SH21B treatment during adipogenesis, which were confirmed by real-time PCR and western blotting. Modulation of the WNT/ß-catenin pathway by SH21B resulted in the nuclear accumulation of ß-catenin. Both intracellular lipid droplet formation and expressions of adipogenic genes including PPARγ, C/EBPα, FABP4 and LPL, which were inhibited by SH21B, were significantly recovered by ß-catenin siRNA transfection. CONCLUSIONS: SH21B modulates components of the WNT/ß-catenin pathway during adipogenesis, and ß-catenin plays a crucial role in the anti-adipogenic mechanism of SH21B.