SUN-048 Maternal Caloric Restriction during Pregnancy Activates the Nrf2 Antioxidant Program in Embryonic Mouse Liver

Obesity and type 2 diabetes in adult life are influenced by the intrauterine environment. The fetus adapts to the environment to which it was exposed, leading potentially to resistance to similar exposures experienced after birth. Studies in both mice and humans suggest that exposure of pregnant females to nutrient deprivation may lead their offspring to develop obesity, insulin resistance and ultimately cardiovascular disease in their adulthood. As the cytoprotective transcription factor Nrf2 (Nfe2l2) is known to be activated upon oxidative and electrophilic stress and has an emerging role in metabolism and specifically in hepatic gluconeogenesis and lipogenesis, we hypothesized that it should be important in the adaptation of the embryos to the metabolic stress induced by maternal caloric restriction. To this end, pregnant C57BL6 mice underwent calorie restriction (CR) by providing them with 50% of the necessary calories per body weight (assessed in pilot experiments) from gestation day 10 to gestation day 16. This CR scheme guarantees the delivery of viable pups that weigh 50% less than the pups whose mothers were fed ad libitum standard chow diet. This CR experiment was performed using either wild-type (WT) or Nrf2 knockout (Nrf2KO) parents. Pregnant females of both genotypes fed ad libitum were used as control. The pregnant females were sacrificed on gestational day 16 and embryos were extracted. Embryonic liver was used for DNA extraction for sex determination by PCR and for RNA preparation to be used for quantitative real-time PCR (qPCR). Statistical significance was set at p