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

Clozapine (CZP) is a second-generation atypical antipsychotic drug used to treat many schizophrenia symptoms, such as positive symptoms, negative symptoms, and recognition disorders. The major side effects of CZP are weight gain and diabetes mellitus, which are risk factors for cardiovascular diseases. However, its mechanism remains unclear.

Curcumin (CUR), a nutraceutical and pharmaceutical substance, is the active ingredient in turmeric, a well-known Indian spice derived from the dried roots of the Curcuma longa plant. The effects of CUR in metabolic syndrome have been studied in several clinical trials. In these trials, CUR improved the lipid profiles and modified the cholesterol-related parameters of the subjects. Furthermore, CUR can improve anthropometric measurements and body composition when taken as part of the diet together with the implementation of appropriate lifestyle interventions.

Adipogenesis is the process of cell differentiation by which pre-adipocytes become adipocytes. Adipogenesis has been one of the most intensively studied models of cellular differentiation. Some studies have reported that CUR suppresses the adipogenic differentiation of 3T3-L1 preadipocytes by downregulating the CCAAT-enhancer binding protein α (C/EBPα)-peroxisome proliferator-activated receptor γ (PPARγ) pathway, which is a major adipogenesis pathway.

The aims of the present study were to determine the mechanism by which CZP induced adipocyte differentiation of 3T3-L1 cells, and whether CUR reduced CZP-induced adipogenesis. Mouse 3T3-L1 preadipocytes were obtained from the European Collection of Cell Cultures (Wiltshire, UK). CZP and CUR were prepared in dimethyl sulfoxide (Me2SO) and added to the growth, initiation, and maturation media from day 3 (time of addition of dexamethasone, IBMX, and insulin) to day 9 (the end of the experiment). Mature adipocytes in the culture were quantified using Lipid Droplets Fluorescence Assay kit, and flow cytometry.

The results showed 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.

In conclusion, this reports showed that CUR could inhibit CZP-induced weight gain and its complications via inhibition of adipocyte differentiation. And the results suggest that CUR has the potential to prevent the side effects of atypical antipsychotic drugs.


Article by Satoru Sakuma, et al, from Osaka University of Pharmaceutical Sciences, Osaka, Japan.

Full access: http://mrw.so/53WyFG

Image by faydasi var, from Flickr-cc.

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