99-OR: Effects of Early Time-Restricted Feeding during Gestation on Offspring Glucose Homeostasis in Mice

Abstract

Time-Restricted Feeding (TRF) is an increasingly common diet that may improve insulin sensitivity. This practice merits study in the setting of pregnancy, as the diet is common, pregnancy represents a critical period for the health of both mother and offspring, and the effects of TRF during pregnancy on maternal gestational health and long-term offspring consequences remain unexamined. To test these effects, female mice were randomized to 6 hours of food availability in the dark cycle (early-time restricted feeding, eTRF), or given 24-hour ad libitum (AL) food access. After one week of acclimatization, females were mated. Food intake and body composition were measured weekly throughout gestation; insulin sensitivity was assessed at day 16 of pregnancy. Offspring birth rate, survival, birthweight, and gestational age were assessed. Body composition and food intake were assessed weekly. After 70 days on a normal diet, all offspring were switched to a 45% high-fat diet (HFD) with continued weekly monitoring. Glucose tolerance and insulin tolerance tests were conducted before and after 10 weeks of HFD feeding. Our data suggests that maternal eTRF does not affect birth weight or gestational age, but does reduce litter size (7.7 pups vs. 6.0 pups) and 3-day pup survival (95% vs. 58%) compared to AL. eTRF offspring had similar insulin and glucose tolerance compared to AL counterparts until adulthood (70 days of age). After 12 weeks of high-fat diet feeding, eTRF males develop concomitant glucose intolerance (auc, p<0.0001) and insulin sensitivity (auc, p=0.006), which was absent in females. These metabolic changes were present despite eTRF males having similar fat mass, body weight, and food intake when compared to AL males. Taken together, these data suggest that eTRF during pregnancy followed by offspring HFD feeding results in male-specific impaired glucose metabolism. Further work planned will evaluate the role of pancreatic islet insulin secretion in vivo and in vitro in future cohorts. Disclosure M. E. Carter: None. N. El habbal: None. D. S. Snyder: None. J. R. Redd: None. B. Gregg: None. D. Bridges: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK107535); University of Michigan