Background: Maternal obesity in known to increase the risk of obesity and diabetes in offspring. However, the effect of maternal obesity on second-generation (F2) offspring is unclear. This study aimed to determine the effect of maternal and grandmaternal obesity on glucose tolerance in rodent offspring.

Methods: 3-week old female C57BL/6 mice were fed either a standard chow (12kJ/g) or high fat diet (HFD; 20 kJ/g) for 6 weeks prior to mating, during pregnancy and throughout lactation. Offspring were then fed either chow or HFD from weaning. At 9 weeks of age, female offspring were mated and her subsequent offspring again weaned to chow or HFD. Intraperitoneal glucose tolerance tests were performed at 18 weeks of age.

Results: Consumption of HFD had a powerful influence on weight and glucose tolerance in offspring. Maternal obesity augmented the effect of HFD on adult offspring obesity. In addition, maternal obesity significantly impaired glucose tolerance in high-fat fed male offspring. Grandmaternal obesity in the absence of maternal obesity had a significant effect on second-generation offspring weight and glucose tolerance. Moreover, grandmaternal obesity had an additive adverse effect to maternal obesity on the glucose tolerance of high-fat fed F2 offspring. There was no effect of maternal or grandmaternal obesity on weight or glucose tolerance in F2 offspring fed a normal chow diet.

Conclusions: Postnatal feeding with HFD has a significant effect on weight and glucose tolerance, which is further compounded by maternal obesity. In addition, grandmaternal obesity in the absence of maternal obesity gives rise to impaired glucose tolerance in offspring fed a HFD. Moreover, a combination of obesity in both grandmother and mother is synergistic to adversely affect glucose tolerance. Thus, two generations of obesity may programme obese offspring towards impaired glucose metabolism. This could propagate the obesity pandemic for future generations.