Atypical antipsychotics such as olanzapine often induce excessive weight gain and type 2 diabetes. However, the mechanisms underlying these drug-induced metabolic perturbations remain poorly understood. Here, we used an experimental model that reproduces olanzapine-induced hyperphagia and obesity in female C57BL/6 mice. We found that olanzapine treatment acutely increased food intake, impaired glucose tolerance, and altered physical activity and energy expenditure in mice. Furthermore, olanzapine-induced hyperphagia and weight gain were blunted in mice lacking the serotonin 2C receptor (HTR2C). Finally, we showed that treatment with the HTR2C-specific agonist lorcaserin suppressed olanzapine-induced hyperphagia and weight gain. Lorcaserin treatment also improved glucose tolerance in olanzapine-fed mice. Collectively, our studies suggest that olanzapine exerts some of its untoward metabolic effects via antagonism of HTR2C.

中文翻译：

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非典型抗精神病药物奥氮平通过靶向血清素2C引起体重增加

非典型抗精神病药（例如奥氮平）通常会导致体重增加过多和2型糖尿病。但是，这些药物引起的代谢扰动的机制仍知之甚少。在这里，我们使用了在雌性C57BL / 6小鼠中重现奥氮平诱导的食欲亢进和肥胖症的实验模型。我们发现奥氮平治疗可急剧增加食物摄入量，损害葡萄糖耐量，并改变小鼠的体育活动和能量消耗。此外，在缺乏血清素2C受体（HTR2C）的小鼠中，奥氮平诱发的食欲亢进和体重增加减弱。最后，我们证明了用HTR2C特异性激动剂lorcaserin治疗可抑制olanzapine所引起的食欲亢进和体重增加。Lorcaserin治疗还改善了奥氮平喂养小鼠的葡萄糖耐量。总的来说，