Maternal Exercise Improves the Metabolic Health of Adult Offspring through Adaptations to Breastmilk
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Date
2019-05
Authors
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Publisher
The Ohio State University
Abstract
Maternal exercise has been shown to improve metabolic health of adult offspring through improvements to glucose tolerance, increased insulin sensitivity, decreased adiposity and other physiological changes. Maternal exercise also negates the deleterious effects of a high fat diet in both male and female offspring. In a world with a growing diabetes and obesity epidemic, it is key to elucidate how these improvements are taking place to develop new therapies and standards of care for pregnant mothers. We hypothesized that maternal exercise alters the composition of breastmilk, which in turn leads to he observed improvements in metabolic health of offspring. To investigate the role of breastmilk, a cross-fostering experiment was performed. Offspring from high-fat fed sedentary dams were crossed with offspring from high-fat fed trained dams (housed in open-wheel cages two weeks prior to and during gestation), forty-eight hours after birth. Both male and female offspring from sedentary dams placed with exercised dams saw improved glucose tolerance, insulin tolerance, decreased adiposity, and reduced body weight through 52 weeks compared to the offspring from trained dams placed with sedentary dams, indicating that the milk from a trained mother plays a significant role in the metabolic improvements in the offspring. Milk samples were then collected from chow fed and high-fat fed, sedentary and exercise-trained dams 7 days after delivering pups and HPLC analysis was performed. The milk oligosaccharide 3’Siallylactose (3’SL) was significantly increased in the exercise-trained dams regardless of their diet, and significantly decreased in the high-fat fed dams. To determine the responsibility of 3’SL in the metabolic improvements in offspring, offspring from sedentary high-fat fed dams were supplemented with either 3’SL or a vehicle during the weaning period. Female 3’SL supplemented offspring had significantly improved glucose tolerance compared to the vehicle fed offspring. To determine if 3’SL was the exercise induced component of responsible for the metabolic health improvements in the offspring, 3’SL-/- mice were exercise-trained. Six-week old female mice were split into four groups: wild-type sedentary, wild-type trained, 3SL-/- trained, and 3SL-/- sedentary. Each exercise-trained mouse completed a treadmill training regimen of one hour at 6.0 m/min and 10% incline 5 days a week, starting two weeks prior to breeding and during gestation. Adult offspring from wild-type exercise-trained dams had improved glucose tolerance and insulin sensitivity compared to adult offspring from sedentary dams. However, there was no difference in metabolic health in offspring from sedentary 3’SL-/- dams compared to exercise-trained 3’SL-/- mice. These exciting data indicate that 3’SL is indeed a key player in propagating the effect of maternal exercise to offspring. Translating these findings to humans could have vast effects to reduce the risk for development of type 2 diabetes.
Description
The presentation of this thesis earned third place in the Health Insights and Interventions category.
Keywords
Maternal Exercise, Breastmilk, 3'sialyllactose, Human milk oligosaccharide, HMO, 3'SL