Yang Fuqi, Zhang Ying, Ju Panyu, Li Leyu, Gong Yu, Zhang Qian, Huang Jiaolong, Duan Peng, Zhou Xingjian
Depatment of Endocrinology, Wuhan University of Science and Technology, Xiangyang, China.
Hubei University of Medicine, Xiangyang, 441000, China.
Sci Rep. 2025 Apr 30;15(1):15198. doi: 10.1038/s41598-025-99473-z.
In recent years, the number of people with type 2 diabetes mellitus (T2DM) has been increasing, and there is obvious familial aggregation of T2DM. Pregestational and gestational diabetes mellitus are the most common chronic conditions during pregnancy. However, the mechanism by which maternal preconception hyperglycaemia affects glucolipid metabolism in the offspring is not fully understood. Zebrafish have been widely used to construct T2DM models. In this study, we established a successful T2DM model of female zebrafish by immersing them in a 2% glucose solution for 28 days. The results showed that female zebrafish in the T2DM group exhibited damage to the ovaries and livers. Fasting blood glucose, insulin, cholesterol and triglycerides were increased in the T2DM group compared to the control group. Moreover, a delayed hatching rate, increased yolk sac area, body length and heart rate and decreased blood flow velocity were observed in the F1 larvae from the maternal zebrafish with T2DM. Glucose, insulin and lipid metabolism were prominently affected in F1 offspring. Importantly, the influence on fasting blood glucose and insulin could persist into adulthood in F1 offspring of zebrafish with maternal T2DM. Transcriptomic results indicated that the signalling pathways of gluconeogenesis, fat digestion and absorption and cholesterol and amino acid metabolism were enriched and perturbed in F1 larvae from zebrafish with maternal T2DM. This study emphasised the impacts of maternal preconception zebrafish hyperglycaemia on glycolipid metabolism in the offspring, transferring the maternal origin of the disease to the preconception stage and providing a reference for further research on the aetiology of glycolipid metabolism disorders.
近年来，2型糖尿病（T2DM）患者数量不断增加，且T2DM存在明显的家族聚集性。孕前糖尿病和妊娠期糖尿病是孕期最常见的慢性疾病。然而，母体孕前高血糖影响子代糖脂代谢的机制尚未完全明确。斑马鱼已被广泛用于构建T2DM模型。在本研究中，我们通过将雌性斑马鱼浸泡在2%葡萄糖溶液中28天，成功建立了T2DM雌性斑马鱼模型。结果显示，T2DM组雌性斑马鱼的卵巢和肝脏出现损伤。与对照组相比，T2DM组的空腹血糖、胰岛素、胆固醇和甘油三酯升高。此外，来自患有T2DM的母体斑马鱼的F1代幼虫孵化率延迟、卵黄囊面积增大、体长和心率增加，血流速度降低。F1代子代的葡萄糖、胰岛素和脂质代谢受到显著影响。重要的是，对空腹血糖和胰岛素的影响在患有母体T2DM的斑马鱼的F1代子代中可持续到成年期。转录组学结果表明，糖异生、脂肪消化与吸收以及胆固醇和氨基酸代谢的信号通路在患有母体T2DM的斑马鱼的F1代幼虫中富集并受到干扰。本研究强调了母体孕前斑马鱼高血糖对子代糖脂代谢的影响，将疾病的母体起源转移到孕前阶段，为进一步研究糖脂代谢紊乱的病因提供了参考。
