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 determined 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 artery 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 and plasma leptin concentrations 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. Exercise prevented dorsal fat gain in Restricted HFD compared to sedentary HFD Restricted rats. Similarly, plasma leptin concentrations were 59% higher in Restricted and 30% higher in Control female rats 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 compared to growth-restricted females on a chow diet and exercise prevented the development of glucose intolerance. Exercise-training prevented the reduced fetal weight in females born small, despite no effect of exercise on placenta weight.
We demonstrated that females born small are at a greater risk of increased adiposity and exacerbated glucose intolerance when exposed to a HFD and these were prevented by the lifestyle intervention of exercise.