Pimozide, a Novel Fatty Acid Binding Protein 4 Inhibitor, Promotes, Adipogenesis of 3T3-L1 Cells by Activating PPAR gamma

Pimozide is a conventional antipsychotic of the diphenylbutylpiperidine class that has been clinically used for over 30 years. The obvious side effect of this drug is weight gain. However, the mechanism of pimozide-induced weight gain is still unknown. In the present study, we identified pimozide as a novel fatty acid binding protein 4 (FABP4) inhibitor using molecular docking simulation as well as biochemical, characterizations. BMS309403, a well-known FABP4 inhibitor, elevated the basal protein levels of PPAR gamma, therefore stimulating adipogenesis in adipocytes. The present study showed that the inhibitory effect of pimozide on FABP4 promoted adipocyte differentiation with the potency proportional to their propensities for weight gain. These effects in adipogenesis by pimozide may help to explain the Weight gain that is frequently observed in patients treated with pimozide.