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.

Pimozide reduces toxic forms of tau in TauC3 mice via 5′ adenosine monophosphate‐activated protein kinase‐mediated autophagy

“…), and FABP4, a protein that regulates activity of PPARγ (peroxisome proliferator‐activated receptor gamma) (Wang et al . ). Thus, the question of how pimozide regulates AMPK for the stimulation of autophagy remains open and needs to be further addressed.…”

“…To summarize, it seems that pimozidemediated AMPK activation is not related to CAMKKb. Recently, many studies about pimozide are being reported; an inhibitor of STAT3 (Chen et al 2015), STAT5 (Nelson et al 2011), and FABP4, a protein that regulates activity of PPARc (peroxisome proliferator-activated receptor gamma) (Wang et al 2015). Thus, the question of how pimozide regulates AMPK for the stimulation of autophagy remains open and needs to be further addressed.…”

Energy transfer from adipocytes to cancer cells in breast cancer

“…Based on the finding of this study, in vitro and in vivo studies in breast cancer showed that adipocyte enhances tumor growth [16,17] or cancer cell proliferation [17,18]. Furthermore, one study showed by using a breast cancer cell line MCF-7, that insulin like growth factor binding protein 2 secretion by adipocyte stimulates breast cancer invasion [19]. Compared to the reverse Warburg effect between breast cancer and fibrous stroma, this theory insists that the stromal cells provide another type of energy, FFA in this case, for the growth of cancer cells [15].…”

“…FABP4 inhibitor was first introduced as a therapeutic agent for type 2 diabetes [20]. The potency of the FABP4 inhibitor was previously verified in several studies [19,23]. We used a well-known FABP4 inhibitor, BMS309403, a cell-permeable and potent inhibitor of FABP4, which targets the fatty acid-binding pocket [24].…”

Estudio de proteínas que unen ácidos grasos (FABPs) de Echinococcus spp.

“…basándose en datos previos obtenidos para otras FABPs de estructura similar, como A-FABP (Cai et al, 2015;Chen et al, 2014;Hertzel et al, 2009;Wang et al, 2015Wang et al, , 2014  Profundizar en los ensayos de silenciamiento de las FABPs como una estrategia adicional para esclarecer el rol que cumplen estas proteínas en Echinococcus spp. Elp-Rv TTGCTGGTAATCAGTCGATC 20 49,7…”