Maternal high-fat diet regulates glucose metabolism and pancreatic β cell phenotype in mouse offspring at weaning

Background. Maternal malnutrition is a critical factor in determining the risk of obesity and glucose intolerance in offspring. However, little is known about the effects of a maternal high-fat diet (HFD) on the beta cell phenotype in offspring, which is a major factor in glucose homeostasis, especially during the early life of offspring. Methods. Dams were randomly fed a HFD (60% kcal from fat) or a chow diet before pregnancy and during gestation and lactation. Glucose metabolism and the beta cell phenotype were assessed in male offspring at weaning. Results. Dams fed a HFD showed impaired glucose tolerance. A HFD predisposed the offspring to increased impairment of metabolic health, including obesity, glucose intolerance and insulin resistance, compared with offspring from chow diet-fed dams. Furthermore, increased islet sizes and islet densities were observed in male offspring from HFD-fed dams at weaning. There were increases in the insulin-positive area, beta cell mass and beta cell proliferation in male offspring from HFD-fed dams at weaning age. Next, we further determined whether a maternal HFD could affect beta cell apoptosis in mouse offspring and found that there was no significant change in beta cell apoptosis between the HFD and control groups. Conclusion. Our study is novel in showing that a maternal HFD predisposes offspring to impaired glucose metabolism and has a profound effect on beta cell mass and proliferation in offspring mice, which is observed in mice as early as at weaning age. However, further study to clarify the underlying mechanisms is warranted.