Linifanib exerts dual anti-obesity effect by regulating adipocyte browning and formation

Obesity is caused by energy imbalance and accompanied by adipocyte hypertrophy and hyperplasia. Therefore, both enhancement of adipocyte energy expenditure and inhibition of adipogenesis are viable ways to combat obesity. Using the Ucp1-2A-luciferase reporter animal model previously reported by us as a screening platform, a chemical compound Linifanib was identified as a potent inducer of UCP1 expression in primary inguinal adipocytes in vitro and in vivo. Signal pathway analyses showed that Linifanib promoted adipocyte browning by attenuating STAT3 phosphorylation. The effects of Linifanib on adipocyte browning were blocked by the compound, SD19, which activates the STAT3 signaling cascade. Linifanib also inhibited adipocyte differentiation, by blocking mitotic clonal expansion, which could be rescued by STAT3 activator. Taken together, our results indicate that Linifanib might serve as a potential drug for the treatment of obesity.