Zebrafish shares common metabolic pathways with mammalian olanzapine-induced obesity

Abstract

Abstract Background 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. Results 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. Conclusion 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.

Keywords

• Danio rerio
• Lipid metabolism
• Metabolic rate
• Olanzapine-induced obesity
• Zebrafish