1395-P: Maternal Exercise during Pregnancy Affects Offspring Adiposity through One Carbon Metabolism Cycle

Abstract

Maternal obesity during pregnancy can adversely affect adult offspring adiposity and insulin resistance. The goal of this study was to determine if maternal exercise mitigates the adverse effects of maternal obesity on offspring health. Female (C57BL/6NJ) mice were fed from weaning a control diet (10%kcal fat; MC n=18) or western diet (45% kcal fat; MW n=15) to induce excess adiposity. After 13 weeks, the mice were bred and maintained on the diets, with (E) and without (S) access to a running wheel (exercise), throughout pregnancy and lactation. Offspring were weaned onto the control diet and fed for 13 weeks; male offspring were studied. Offspring from MWE dams had greater (p<0.05) retroperitoneal and mesenteric adipose tissue than offspring from MWS dams. This was not observed in offspring from dams fed the control diet. Offspring from exercised dams had lower glucose-stimulated insulin secretion compared to those from sedentary dams, independent of maternal diet. No differences in glucose and insulin tolerance were observed. One carbon metabolism is required for several physiological processes including DNA synthesis, amino and lipid metabolism, and the generation of methyl groups. Disturbances in one carbon metabolism occur in obesity. We hypothesized that maternal exercise mitigates the adverse effects of maternal obesity on offspring adiposity through changes in one carbon metabolism. MCE offspring had lower serum total homocysteine (6.3μmol/L) compared to MCS offspring (9.4μmol/L). This was not observed in the offspring from western diet-fed dams. Offspring from western diet-fed dams had higher hepatic methylenetetrahydrofolate reductase (Mthfr) mRNA expression compared to offspring from control diet-fed dams. Offspring from dams that exercised also had higher hepatic Mthfr mRNA; the highest expression was observed in MWE offspring. The findings from this study suggest that one carbon metabolism may play a role in developmental programing of offspring adiposity. Disclosure N. Boonpattrawong: None. A. Mehran: None. I. Laher: None. A.M. Devlin: None. Funding Canadian Institutes of Health Research