Intrauterine Hyperglycemia Induces Dysregulated Lipid Metabolism In Adult Male Mouse Offspring

Exposure to an abnormal intrauterine environment is thought to be associated with lipid metabolism disorder in offspring.In this study,we aimed to determine the effects of antenatal exposure to intrauterine hyperglycemia on mouse offspring’s lipid metabolism and the potential mechanism.Pregnant ICR mice in the gestational diabetes mellitus(GDM)group were injected with streptozotocin.Pups were allocated to control group(F1-C)and GDM group(F1-D).Both male and female offspring in Fl-D group showed significantly lower birth weight than offspring in F1-C group(P<0.001).Male offspring in Fl-D group presented increased body weight since 12 weeks of age,while female showed no difference in body weight.At the age of 8 and 20 weeks,male offspring in F1-D group showed marked dyslipidemia and increased liver and fat weight,whereas female presented slight changes compared to control offspring.Oil-Red-O staining detected an increased level of lipid droplets in liver tissues of male offspring in Fl-D group at the age of 8 weeks,confirmed by increased levels of hepatic triglyceride and total cholesterol,while no alterations were observed in female mice.At the age of 8 weeks,male offspring in F1-D group showed increased expression levels of genes involved in fatty acid synthesis and cholesterol synthesis,along with decreased expression levels of genes related to fatty acid oxidation and cholesterol transportation in liver.Taken together,our study suggests that intrauterine hyperglycemia exposure may induce hepatic steatosis,obesity,and dyslipidemia in adult male offspring.