Late-Onset Exercise in Female Rat Offspring Ameliorates the Detrimental Metabolic Impact of Maternal Obesity

Rising rates of maternal obesity/overweight bring the need for effective interventions in offspring. We observed beneficial effects of postweaning exercise, but the question of whether late-onset exercise might benefit offspring exposed to maternal obesity is unanswered. Thus we examined effects of voluntary exercise implemented in adulthood on adiposity, hormone profiles, and genes involved in regulating appetite and metabolism in female offspring. Female Sprague Dawley rats were fed either normal chow or high-fat diet (HFD) ad libitum for 5 weeks before mating and throughout gestation/lactation. At weaning, female littermates received either chow or HFD and, after 7 weeks, half were exercised (running wheels) for 5 weeks. Tissues were collected at 15 weeks. Maternal obesity was associated with increased hypothalamic inflammatory markers, including suppressor of cytokine signaling 3, TNF-α, IL-1β, and IL-6 expression in the arcuate nucleus. In the paraventricular nucleus (PVN), Y1 receptor, melanocortin 4 receptor, and TNF-α mRNA were elevated. In the hippocampus, maternal obesity was associated with up-regulated fat mass and obesity-associated gene and TNF-α mRNA. We observed significant hypophagia across all exercise groups. In female offspring of lean dams, the reduction in food intake by exercise could be related to altered signaling at the PVN melanocortin 4 receptor whereas in offspring of obese dams, this may be related to up-regulated TNF-α. Late-onset exercise ameliorated the effects of maternal obesity and postweaning HFD in reducing body weight, adiposity, plasma leptin, insulin, triglycerides, and glucose intolerance, with greater beneficial effects in offspring of obese dams. Overall, hypothalamic inflammation was increased by maternal obesity or current HFD, and the effect of exercise was dependent on maternal diet. In conclusion, even after a significant sedentary period, many of the negative impacts of maternal obesity could be improved by voluntary exercise and healthy diet.