Olanzapine is one of the most prescribed antipsychotic agents in the pharmacotherapy of psychiatric illness; however, it is associated with multiple side effects primarily obesity. Multiple investigations have been made to model the olanzapine-induced obesity in rodent models which was found to be dose-dependent, gender-dependent, and species-dependent. Danio rerio is a choice of an animal model to understand the pathogenesis of multiple diseases. The present study dealt to understand the olanzapine-associated obesity in zebrafish using in silico and wet-lab experimental protocols by performing gene set enrichment analysis, phylogeny comparison of receptors, and assessing the effect of olanzapine on metabolic rate, lipid metabolism, body weight, and food intake in zebrafish. The metabolic pathway was predicted to be majorly modulated by olanzapine in human, rat, mouse, and zebrafish. A clade of receptors of rat, mouse, and human receptor for feeding and satiety center was found similar to zebrafish. The decrease in lipid metabolism was observed in zebrafish larvae if exposed to olanzapine solution. Similarly, there was a significant decrease in metabolic rate in 200 μM and 400 μM concentration of olanzapine. Enrichment analysis predicted the probable modulation of metabolic pathways in zebrafish if exposed to olanzapine. Further, olanzapine was identified to play a prime role in decreasing lipid metabolism and metabolic rate and increasing food intake and weight gain in zebrafish which suggests the validation of this model for olanzapine-induced obesity.

中文翻译：

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斑马鱼与哺乳动物奥氮平诱发的肥胖症具有共同的代谢途径

奥氮平是精神疾病药物治疗中处方最广泛的抗精神病药物之一；但是，它与多种肥胖相关，主要是肥胖。在啮齿动物模型中已经进行了许多研究来模拟奥氮平诱发的肥胖，该模型被发现具有剂量依赖性，性别依赖性和物种依赖性。Danio rerio是一种了解多种疾病发病机理的动物模型。本研究通过进行基因组富集分析，受体的系统发育比较以及评估奥氮平对代谢率，脂质代谢，体重的影响，采用计算机模拟和湿实验室实验方案来了解斑马鱼中与奥氮平相关的肥胖症和斑马鱼的食物摄入量。预测在人，大鼠，小鼠和斑马鱼中，该代谢途径主要受奥氮平的调节。发现大鼠，小鼠和人类受体的进化枝与斑马鱼相似，它们能喂养和饱食。如果暴露于奥氮平溶液中，在斑马鱼的幼虫中观察到脂质代谢的降低。同样，奥氮平的浓度为200μM和400μM时，代谢率也明显降低。富集分析预测，如果暴露于奥氮平，斑马鱼的代谢途径可能会发生调节。此外，已确定奥氮平在降低脂质代谢和代谢率以及增加斑马鱼的食物摄入和体重增加中起主要作用，这表明该模型可用于奥氮平诱导的肥胖症的验证。小鼠，发现人类的食物和饱腹感受体类似于斑马鱼。如果暴露于奥氮平溶液中，在斑马鱼的幼虫中观察到脂质代谢的降低。同样，奥氮平的浓度为200μM和400μM时，代谢率也明显降低。富集分析预测，如果暴露于奥氮平，斑马鱼的代谢途径可能会发生调节。此外，已确定奥氮平在降低脂质代谢和代谢率以及增加斑马鱼的食物摄入和体重增加中起主要作用，这表明该模型可用于奥氮平诱导的肥胖症的验证。小鼠，发现人类的食物和饱腹感受体类似于斑马鱼。如果暴露于奥氮平溶液中，在斑马鱼的幼虫中观察到脂质代谢的降低。同样，奥氮平的浓度为200μM和400μM时，代谢率也明显降低。富集分析预测，如果暴露于奥氮平，斑马鱼的代谢途径可能会发生调节。此外，已确定奥氮平在降低脂质代谢和代谢率以及增加斑马鱼的食物摄入和体重增加中起主要作用，这表明该模型可用于奥氮平诱导的肥胖症的验证。奥氮平的浓度为200μM和400μM时，代谢率显着降低。富集分析预测，如果暴露于奥氮平，斑马鱼的代谢途径可能会发生调节。此外，已确定奥氮平在降低脂质代谢和代谢率以及增加斑马鱼的食物摄入和体重增加中起主要作用，这表明该模型可用于奥氮平诱导的肥胖症的验证。奥氮平的浓度为200μM和400μM时，代谢率显着降低。富集分析预测，如果暴露于奥氮平，斑马鱼的代谢途径可能会发生调节。此外，已确定奥氮平在降低脂质代谢和代谢率以及增加斑马鱼的食物摄入和体重增加中起主要作用，这表明该模型可用于奥氮平诱导的肥胖症的验证。