Olanzapine enhances adipogenesis and suppresses lipolysis in 3T3-L1 adipocytes under low-glucose and weak differentiation/maturation conditions

Olanzapine, a second-generation antipsychotic used in the treatment of schizophrenia, is classified as a multi-acting receptor-targeted antipsychotic. Abnormal weight gain is one of the most common side effects of this drug, along with an increased appetite and food intake. However, weight gain has also been reported in patients taking olanzapine without an increase in appetite. Olanzapine has been reported to be directly associated with enhanced adipogenesis; however, whether olanzapine increases lipid content in adipocytes under weak stimulus conditions, such as low glucose concentrations and weak differentiation and/or maturation conditions, is poorly understood. The present study examined the stimulatory effect of olanzapine during the differentiation and maturation of 3T3-L1 pre-adipocytes under low-glucose and weak stimulation conditions by evaluating the expression levels of PPAR gamma by western blotting and oil red O staining. Western blotting revealed that olanzapine suppressed perilipin phosphorylation, which is an important lipolysis step in adipocytes. The findings of the present study provide novel insights to explain weight gain in patients taking olanzapine but not presenting with increased food intake.