Inhibitory effect of t10 c12 conjugated linoleic acid (CLA) isomer on clozapine induced adipogenesis in 3T3‐L1 cells

Abstract

Atypical (second generation) antipsychotics such as clozapine have become the primary choice of medication for treating psychosis. An unfortunate side‐effect of these medications is weight gain, a condition often associated with the development of metabolic disorders such as diabetes. Factors thought to facilitate this weight gain include increased food intake, reduced energy expenditure, and impaired pre‐adipocyte differentiation. CLA, specifically the t10 c12 isomer, has been known to suppress adipogenesis both in vitro and in vivo model. Thus we tested the effect of the t10 c12 CLA on clozapine induced adipogenesis in 3T3‐L1 cells. 3T3‐L1 pre‐adipocytes were differentiated by the addition of insulin (1μg/ml), dexamethasone (1μM), IBMX (10mM), and 10% FBS in DMEM medium. Cells were treated with or without clozapine (10 and 20μM) and/or t10 c12 CLA (50μM). Lipid accumulation was measured by Oil‐red O staining and intracellular triacylglyceride contents were analyzed. mRNA level of the lipid metabolism related transcription factors were measured by RT‐PCR. Cells treated with clozapine alone showed significant increase in lipid accumulation compared to control. However, increased lipid accumulation by clozapine was significantly prevented in cells treated with CLA. mRNA level of fatty acid synthase (FAS), acetyl‐CoA carboxylase (ACC), uncoupling protein‐2 (UCP‐2), and peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) in the cells treated with CLA were significantly decreased by t10 c12 CLA with or without treatment of clozapine. These results suggest that CLA may be used to prevent fat accumulation associated with antipsychotic administration.