Induction of subcutaneous adipose proliferation by olanzapine in rodents

Weight gain induced by atypical antipsychotics causes a serious health concern in the treatment of schizophrenic patients. In the present study chronic treatment of female Wistar rats with olanzapine caused weight gain, but limited effect on food intake. A dramatic drug-induced morphological change of the subcutaneous adipose tissue was observed, i.e. development of a pinkish coloration with the appearance of a "fish egg"-like texture. Histological examination revealed a massive increase in the proliferation of undifferentiated adipocytes. Such proliferation was detected as early as the third day after olanzapine treatment. The changes progressed in a time- and dose-dependent manner. The proliferation of adipose tissue was detected in rats treated with olanzapine independent of increases in weight gain. Protein profiles of the adipose tissue were also altered by olanzapine. These results suggest that olanzapine-induced weight gain may be not solely due to an effect on behavioural satiety. The potential involvement of adipose neuronal input and proliferation are discussed.