Authors: 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

PMID: 25437245

DOI: 10.1021/cn5002107

Publication Type: Research Support, Non-U.S. Gov’t

ISSN: 1948-7193

Journal Title: ACS chemical neuroscience

Publication Date: 2015 Feb 18

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.

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