Differential impact of maternal overnutrition and undernutrition on offspring glucose homeostasis

To test the hypothesis that maternal undernutrition exerts a greater effect on offspring metabolic function compared to maternal overnutrition, female rats (n=10 per group) were subjected to a high calorie diet or 50 % global nutrient restriction relative to control rats on standard rat chow, for 8 weeks prior to pregnancy and during pregnancy. Birth weight was determined on the day dams were found with pups. At 3 months of age, offsprings fasting blood glucose, serum insulin and triglyceride levels as well as glucose tolerance and insulin sensitivity were determined. A 50 % calorie restriction caused a significant weight loss in the under-nourished dams but those on high calorie diet had similar body weight as control rats. Maternal overnutrition and undernutrition significantly lowered birth weight, indicating intra-uterine growth restriction in these animals. Fasting blood glucose was significantly higher in female offspring of over-nourished dams, but neither maternal overnutrition nor undernutrition affected offsprings glucose tolerance. Male offspring of dams exposed to maternal overnutrition or undernutrition had a significantly higher insulin level compared to control, whereas female offspring were unaffected. The development of hyperinsulinaemia in male offspring of undernourished dams was accompanied by reduced insulin sensitivity. This study demonstrates that early-life exposure to two extreme ends of the nutritional plane is associated with similar birth weight outcome but different metabolic phenotype in adulthood. Evidence of insulin resistance only in male offspring of under-nourished dams indicates differences in sex-specific metabolic effect of maternal undernutrition compared to overnutrition.