Although clozapine (CZP), which is used for schizophrenia treatment, causes weight gain, the mechanism remains unclear. We recently reported that the naturally occurring compound curcumin (CUR) suppresses adipogenesis in 3T3-L1 cells. The aims of the present study were to determine the mechanism by which CZP induces adipocyte differentiation of 3T3-L1 cells, and whether CUR reduces CZP-induced adipogenesis. We found that cells grown in the presence of CZP had significantly higher triacylglycerol levels, numbers of lipid-filled adipocytes, and mRNA expression levels of CCAAT-enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) than those grown without CZP. Treatment with CZP plus CUR resulted in major reductions in these four parameters. These results suggest that CZP enhances adipogenesis in 3T3-L1 cells via the C/EBPα-PPARγ pathway and that by interrupting CZP’s effects, CUR might be a potent agent for preventing CZP-induced weight gain.
KeywordsClozapineCurcuminAdipocyte Differentiation3T3-L1 CellAtypical Antipsychotic Drug
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