Abstract
Atypical antipsychotics such as olanzapine 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 syndromes. To elucidate the mechanism of impairing lipid and glucose metabolism, we examined the glucose and lipid metabolism in olanzapine treated 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 various concentrations of olanzapine (0, 5, 10 and 20μM). Lipid accumulation was estimated by measuring intracellular triacylglyceride contents. Level of mRNA and protein expression of the lipid metabolism related transcription factors were measured by RT‐PCR and Western Blot analysis, respectively. Cells treated with olanzapine showed significant and dose dependent increase in lipid accumulation. 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 olanzapine were significantly increased in dose dependent manner.
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