Intrauterine growth restriction programs adult metabolic disease, which is exacerbated with “second hits” such as pregnancy and overweight/obesity in females born small. We have recently reported that the physiological challenge of pregnancy unmasks glucose intolerance in females born small. This study will determine if the known adverse physiological adaptations to pregnancy in rats born small are exacerbated with a high fat diet (HFD) and whether endurance exercise training can prevent these complications.
Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham (Control) surgery on E18 in Wistar-Kyoto rats. Female offspring were fed a chow or HFD (43% kcals from fat) from 5 weeks of age to mating (20 weeks) and throughout pregnancy. Female rats were exercised on a treadmill 4 weeks before mating and throughout pregnancy. Glucose tolerance test was performed (E18) and dorsal fat weights, plasma leptin concentrations and pancreatic β-cell and islet mass were measured at E20.
Restricted and Control female rats that were exposed to a HFD were heavier with ~30% more dorsal fat than females on a chow diet and exercise prevented dorsal fat gain. Similarly, plasma leptin concentrations were 59% higher in Restricted and 30% higher in Control females on a HFD compared to females on Chow diet. HFD exacerbated the pre-existing glucose intolerance (+15% area under curve) in pregnant females born small and exercise prevented the development of glucose intolerance. However, there were no difference in β-cell mass and islet mass across the groups.
We demonstrated that females born small are at a greater risk of glucose intolerance when exposed to a HFD and these were prevented by the lifestyle intervention of exercise. Lack of difference observed in β-cell mass in pregnant females may reflect a long-term protective effect of pregnancy despite having different treatment and diet.