title: Pimozide, a novel fatty acid binding protein 4 inhibitor, promotes adipogenesis of 3T3-L1 cells by activating PPARγ.
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.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong , Shatin, Hong Kong SAR, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Huang-Quan
authors.initials: HQ
authors.lastname: Lin
authors.forename: Wai-Kit
authors.initials: WK
authors.lastname: Law
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Liang
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Zhang
authors.forename: Jian-Shu
authors.initials: JS
authors.lastname: Hu
authors.forename: Tsz-Ming
authors.initials: TM
authors.lastname: Ip
authors.forename: Mary Miu-Yee
authors.initials: MM
authors.lastname: Waye
authors.forename: David Chi-Cheong
authors.initials: DC
authors.lastname: Wan
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010868:Pimozide / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology
chemical_list: C559288:2-(2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy)acetic acid; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D001713:Biphenyl Compounds; D002491:Central Nervous System Agents; C493410:FABP4 protein, human; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D011720:Pyrazoles; D010868:Pimozide
keywords: PPARγ; Pimozide; adipogenesis; fatty acid binding protein 4 inhibitor; molecular docking