Curcumin Inhibits Adipogenesis Elicited by Clozapine in 3T3-L1 Cells

Satoru Sakuma,Kaho Tsujimoto,Tetsuya Kohda,Yohko Fujimoto,Tomohiko Sano,Chisato Noda,Maki Sumida,Ayaka Nakamura,Maimi Kobayashi,Asami Sakabe

doi:10.4236/fns.2018.95044

Abstract

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.

Highlights

Clozapine (CZP) is a second-generation atypical antipsychotic drug used to treat many schizophrenia symptoms, such as positive symptoms, negative symptoms, and recognition disorders
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
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

Summary

Introduction

Clozapine (CZP) is a second-generation atypical antipsychotic drug used to treat many schizophrenia symptoms, such as positive symptoms, negative symptoms, and recognition disorders. It has been suggested that second-generation atypical antipsychotic drugs cause body weight gain by affecting the receptors of the central nervous system and by directly affecting peripheral adipogenesis [3]-[8]. Many phytochemical compounds have been found to have a high capacity to act against various disorders, including metabolic syndrome. One of these substances, curcumin (CUR), a nutraceutical and pharmaceutical, is the active ingredient in turmeric, a well-known Indian spice derived from the dried roots of the Curcuma longa plant. CUR can improve anthropometric measurements and body composition when taken as part of the diet together with the implementation of appropriate lifestyle interventions [11]

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