210 Restricted Maternal Nutrition: Impacts on Fetal Development and Metabolism in Sheep Free

Adequate nutrition is important for proper growth and metabolism. This is even more important during gestation when insults to the fetus can negatively impact fetal growth and development with persistent effects into adulthood. Using a sheep model, we have demonstrated that maternal restricted feeding (60% of National Research Council requirements) during gestation reduced growth in offspring and muscle fiber cross-sectional area. These changes in growth are associated with reduced stem cell (satellite cells and mesenchymal stem cells) population and function. Offspring of restricted-fed mothers also displayed altered metabolism indicated by increased insulin resistance, leptin dysregulation, and reduced circulating metabolic and growth factors. Based on these persistent negative effects of maternal diet on offspring postnatal growth and metabolism, we evaluated the impacts during fetal growth on whole body and tissue-specific metabolism and the impact of maternal realimentation during gestation. Nutrient restriction caused changes in metabolic pathways in a tissue specific manner in muscle, liver, and blood demonstrating the ability of maternal diet to program offspring metabolism in highly metabolic tissues. Several pathways involved in amino acid, lipid, carbohydrate, and transsulfuration/methionine metabolism were altered in all 3 tissues, demonstrating the whole-body effects of maternal diet on offspring metabolism. Interestingly, realimentation alleviated some of the effects of nutrient restriction on offspring metabolic pathways. In summary, maternal nutrient restriction during gestation negatively affects offspring fetal growth with persistent effects into adulthood which may be caused by changes in stem cell function and key metabolic pathways during fetal development.