Effects of maternal obesity and voluntary exercise prior to and during pregnancy on rat offspring

摘要

Evidence from animal models and clinical data suggest that maternal obesity programs a range of detrimental effects in offspring. Limiting gestational weight gain may be a useful strategy to reduce these effects. This thesis investigated the impact of voluntary exercise during pregnancy on health outcomes in offspring of obese and lean mothers. Female Sprague-Dawley rats were fed chow (C n=28) or high fat (F n=32) diet for 6 weeks. Ten days before mating, half of each group were offered voluntary exercise with a running wheel (CE/FE); the others remained sedentary (CS/FS). Wheel access continued until parturition. Pup body weight (BW) was monitored and two pups from each mother were killed at postnatal day (PND)19. Thereafter siblings were fed chow. At 5-6 weeks, male pups were tested for anxiety on the Elevated Plus Maze (EPM); all offspring were killed at 13 weeks (adult) for metabolic assessment.Lean and obese mothers showed similar modest levels of exercise with no significant effect on maternal BW. At PND1, lean exercised mothers had lighter male and female pups with no effect in those from obese mothers. At PND19, maternal obesity increased offspring BW and adiposity with no effect of exercise. Exercise reduced insulin concentrations in males, with reduced glucose in male FE pups. In males, maternal obesity significantly decreased muscle MYOD1 and GLUT4 mRNA expression and these were normalised by exercise. Maternal exercise upregulated adipose GLUT4, IL6, TNFα, and PGC1α mRNA expression in CE offspring. Maternal obesity had no effect on anxiety-like behavior while CE offspring showed increased anxiety-like behavior. Adult FS males had higher plasma insulin, leptin and triglyceride concentrations, which were normalised by maternal exercise, while in females only the insulin concentration was raised. In males, hippocampus TLR4, FTO and IL-1β mRNA expression were upregulated by maternal obesity, and normalised by exercise.Taken together, maternal obesity increased the risk of metabolic disease in offspring, with higher BW, adiposity, hyperleptinemia, hyperinsulinemia and increased brain inflammatory markers. Modest levels of maternal exercise appeared to decrease the metabolic risk induced by maternal obesity. Exercise had sex-specific benefits that were more marked in male offspring.