The mechanism of maternal inheritance of glycolipid metabolism disorder in a zebrafish model of type 2 diabetes

Abstract

Abstract 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.

Keywords

• T2DM
• Maternal exposure
• Glycolipid metabolism
• Intergenerational effect
• Zebrafish