Garcinia cambogia suppresses adipogenesis in 3T3-L1 cells by inhibiting p90RSK and Stat3 activation during mitotic clonal expansion

Obesity is associated with an increase in adipose tissue, which is mediated by hyperplasia and hypertrophy. Therefore, inhibiting cell proliferation during mitotic clonal expansion (MCE) is one of the major strategies for preventing obesity. The antagonistic effects ofGarcinia cambogia(G.cambogia) on obesity have been studied in animal experimental models. However, the effects ofG.cambogiaextract on MCE, and the underlying molecular mechanisms, are poorly understood. In this study, 3T3-L1 cells were used to investigate whetherG.cambogiaextract affected cell proliferation during MCE and to identify target molecules for any anti-adipogenic activity.G.cambogiaextract suppressed isobutylmethylxanthine and dexamethasone-and-insulin (MDI)-induced adipogenesis at an early stage by attenuating MCE. InG.cambogiaextract-treated preadipocytes, MDI-induced cell proliferation and cell cycle progression were inhibited by G(0)/G(1)arrest due to an increase in p21 and p27 expression, and inhibition of cyclin-dependent kinase 2, cyclin E1 expression, and retinoblastoma (Rb) phosphorylation. In addition, the MDI-induced phosphorylation and subsequent translocation into the nucleus of p90 ribosomal S6 kinase (p90RSK) and signal transducer and activator of transcription (Stat) 3 were suppressed. Specific inhibitors of p90RSK (FMK) and Stat3 (stattic) regulated cell proliferation and adipogenesis. In conclusion, this study demonstrated thatG.cambogiaextract inhibited MCE by regulating p90RSK, Stat3, and cell cycle proteins, leading to G(0)/G(1)arrest. These findings provide new insight into the mechanism by whichG.cambogiasuppresses adipocyte differentiation and show that p90RSK is critical for adipogenesis as a new molecular target.