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Maternal exercise mitigates the adverse effects of obesity on adult offspring cardiometabolic health

University of British Columbia

Background: Maternal obesity during pregnancy is associated with insulin resistance and vascular endothelial dysfunction (an early indicator of vascular damage) in offspring. However, it is unclear whether maternal exercise can mitigate the adverse effects of maternal obesity. My thesis research tested the hypothesis that maternal exercise during pregnancy and lactation will mitigate the adverse effects of maternal obesity on offspring health. Methods: Female (C57BL/6N) mice (dams) were fed a control diet (control dams; 10% kcal fat) or a western diet (obese dams; 45% kcal fat) from weaning for 13 weeks to induce excess adiposity and glucose intolerance prior to pregnancy. Dams were bred at age 16 weeks to age-matched males C57BL/6N mice fed the control diet. One week prior to breeding, the female mice were provided with a running wheel in the cage (voluntary exercise) or no wheel. Two groups of male offspring were studied: i) age postnatal day 7 (P7); and ii) adults weaned on to the control or western diet and fed for 14 weeks. Results: Adult offspring from obese dams that exercised had improved vascular endothelial-dependent function, but this was only observed in the offspring fed the western diet. This was accompanied by alterations in aorta and liver one-carbon metabolism. At P7, male pups from exercised dams had improved  cell function compared to pups from sedentary dams. In the adult offspring, exercise improved glucose tolerance in offspring fed the western diet that were from obese dams. Unexpectedly, maternal exercise increased adiposity in adult offspring fed the control diet that were from obese dams but no differences in glucose homeostasis were observed. The alterations in adiposity by maternal exercise were accompanied by differential DNA methylation in adipocytes. In the dams, exercise improved insulin sensitivity and altered aorta and liver one-carbon metabolism, suggesting that the phenotype observed in the offspring may be due to obesity and exercised-induced changes in one-carbon metabolism in the dams. Conclusion: My findings demonstrate that maternal exercise prevented vascular dysfunction, improved glucose homeostasis, and altered adiposity in the male offspring and involves tissue-specific alterations in one-carbon metabolism and DNA methylation.

Text

2020-08-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/75754

Pathology and Laboratory Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/