Abstract
Olanzapine is an antipsychotic drug. Weight gain is a typical side effect of olanzapine, but its mechanism is unknown. Leptin is a centrally acting anti-obesity hormone, involved in attenuating obesity. It has been shown that leptin resistance is involved in diet-induced obesity. In the present study, we hypothesized that mechanisms of olanzapine on weight gain may involve leptin resistance.We performed leptin stimulation on SHSY-5Y-ObRb cells expressing leptin receptor and examined the effect of olanzapine on phosphorylation of STAT3, an indicator of leptin signaling. We found that in the presence of olanzapine, leptin-induced phosphorylation of STAT3 was inhibited in a dose-dependent manner. On the other hand, olanzapine did not inhibit IL-6-induced STAT3 phosphorylation. These results suggest that the inhibition of STAT3 phosphorylation may be leptin receptor specific. In order to investigate the possibility that olanzapine induces leptin resistance through the translation synthesis, we conducted the same experiment in the presence of the translation inhibitor, cycloheximide. As a result, cycloheximide had no effect on the inhibition of STAT3 phosphorylation by olanzapine. This indicates that the inhibition of leptin-induced STAT3 phosphorylation by olanzapine may not involve protein synthesis.
