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 of Garcinia cambogia (G. cambogia) on obesity have been studied in animal experimental models. However, the effects of G. cambogia extract on MCE, and the underlying molecular mechanisms, are poorly understood. In this study, 3T3‐L1 cells were used to investigate whether G. cambogia extract affected cell proliferation during MCE and to identify target molecules for any anti‐adipogenic activity. G. cambogia extract suppressed isobutylmethylxanthine and dexamethasone‐and‐insulin (MDI)‐induced adipogenesis at an early stage by attenuating MCE. In G. cambogia extract‐treated preadipocytes, MDI‐induced cell proliferation and cell cycle progression were inhibited by G0/G1 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 that G. cambogia extract inhibited MCE by regulating p90RSK, Stat3, and cell cycle proteins, leading to G0/G1 arrest. These findings provide new insight into the mechanism by which G. cambogia suppresses adipocyte differentiation and show that p90RSK is critical for adipogenesis as a new molecular target. Garcinia cambogia extract inhibited mitotic clonal expansion and suppressed 3T3‐L1 preadipocyte proliferation at an early stage of adipocyte differentiation by modulating p90 ribosomal s6 kinase, signal transducer and activator of transcription 3, and the cell cycle proteins, such as p21, p27, leading to G0/G1 arrest.