Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene – a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity—and provide new insights into how endogenous metabolites change following limonene treatment. Using HFD-fed male and female zebrafish, we were able to develop an animal model of T2D and identify several endogenous metabolites that might be used as diagnostic biomarkers for diabetes. The endogenous metabolites in males and females were different, even though both genders had high blood glucose levels and a high BMI. Treatment with limonene prevented high blood glucose levels and improved in diabesity zebrafish by limonene, through reversal of the metabolic changes caused by HFD in both genders. In addition, limonene was able to reverse the elevated expression of AKT during HFD.

斑马鱼多年来一直被用作糖尿病和肥胖症药理学研究的模型动物。高脂饮食（HFD）、链脲佐菌素和四氧嘧啶注射以及葡萄糖浸泡都已被用来诱发斑马鱼糖尿病和肥胖。目前，研究通常使用雄性和雌性斑马鱼，这可能会影响结果，因为雄性和雌性斑马鱼在生物学上不同。本研究旨在利用柠檬烯（一种天然产物，在体外和体内治疗糖尿病和肥胖方面显示出一些有希望的结果）来研究雄性和雌性糖尿病斑马鱼代谢物之间的差异，并为内源代谢物如何变化提供新的见解柠檬烯处理后。使用 HFD 喂养的雄性和雌性斑马鱼，我们能够开发 T2D 动物模型，并鉴定出几种可用作糖尿病诊断生物标志物的内源代谢物。尽管男性和女性的血糖水平和体重指数都较高，但其内源代谢物是不同的。柠檬烯治疗可预防高血糖水平，并通过逆转 HFD 引起的雌雄代谢变化，改善斑马鱼的糖尿病。此外，柠檬烯能够逆转 HFD 期间 AKT 表达的升高。