Maternal Fructose Intake During Pregnancy Induced the Hepatic Glucose Homeostasis Imbalance in the Offspring by Inhibiting Glucokinase

The global incidence of metabolic disorders has shown a significant upward trend, with growing evidence suggesting a strong association between their development and maternal environmental factors during gestation, including dietary patterns. This study investigated the effects of maternal fructose consumption during pregnancy on hepatic glucose metabolism in male mouse offspring. The results revealed that downregulation of Glucokinase expression was closely associated with impaired glucose metabolism in the liver tissue of the offspring. Furthermore, DNA Methyltransferase 3 beta (DNMT3B)-mediated hypermethylation of the Glucokinase (GCK, protein: GK) promoter region was responsible for this transcriptional repression. This study established that maternal fructose intake during pregnancy led to reduced GK expression through DNMT3B-dependent epigenetic modifications, resulting in abnormal glucose metabolism. Importantly, pharmacological intervention with a GK activator effectively ameliorated these metabolic abnormalities. Besides, the expression of DNMT3B was regulated by CCAAT Enhancer Binding Protein Beta (C/EBPβ) at the transcriptional level. In brief, this study demonstrated that maternal fructose intake has a negative effect on glucose metabolism in the liver of offspring and highlights the importance of dietary guidance during pregnancy and diabetes prevention.

DNA methylation; fructose; glucokinase; liver glucose metabolism; offspring.