Pimozide, a novel fatty acid binding protein 4 inhibitor, promotes adipogenesis of 3T3-L1 cells by activating PPARγ

Yan Wang, Huang Quan Lin, Wai Kit Law, Wei Cheng Liang, Jin Fang Zhang, Jian Shu Hu, Tsz Ming Ip, Mary Miu Yee Waye, David Chi Cheong Wan

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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 PPARγ, 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.

Original languageEnglish (US)
Pages (from-to)211-218
Number of pages8
JournalACS Chemical Neuroscience
Volume6
Issue number2
DOIs
StatePublished - Feb 18 2015

Keywords

  • PPARγ
  • Pimozide
  • adipogenesis
  • fatty acid binding protein 4 inhibitor
  • molecular docking

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