Fetal programming from sub-lethal radiation: glucose metabolism in the liver and brown adipose tissue
Master of Science
SubjectIonizing radiation exposure
Radiation exposure during pregnancy
Prenatal radiation exposure in humans
Brown adipose tissue
MetadataShow full item record
Exposure to ionizing radiation contributing to negative health outcomes is a widespread concern among the public, scientific community, and workers in the nuclear energy industry and diagnostic imaging field. However, the impact of sub-lethal exposures remains contentious particularly in pregnant women who represent a vulnerable group. The fetal programming hypothesis states that an adverse in-utero environment or stress during development of an embryo or fetus can result in permanent physiologic changes often resulting in progressive metabolic dysfunction with age. Various models of fetal programming present similar outcomes with offspring demonstrating alterations in birth weight. Low birth weight predisposes offspring to insulin resistance and impaired glucose metabolism. To assess the effects of sub-lethal dose radiation on fetal programming of glucose metabolism, pregnant C57Bl/6J mice were irradiated at 1000 mGy and compared to a sham irradiated group. Female offspring born to dams irradiated at 1000 mGy had: 1) increased liver weights, 2) increased hepatic protein expression of suppressor of cytokine signaling 3 (SOCS3) and phosphoenolpyruvate carboxykinase (PEPCK), and 3) increased 18Ffluorodeoxyglucose (18F-FDG) uptake in interscapular brown adipose tissue (IBAT) measured by positron emission tomography (PET). Male offspring born to irradiated dams showed non-significant reductions in SOCS3 and PEPCK protein expression in the liver and increased hepatic triglycerides. Radiation exposure to 1000 mGy caused no change in plasma triglycerides, however significant sex differences were observed. Female IBAT phosphorylated protein kinase B (Akt) to total Akt ratio and phosphorylated glycogen synthase kinase 3 beta (GSK3b) to total GSK3b ratio did not increase significantly with treatment suggesting insulin signaling is not responsible for the increase in tissue specific 18Ffluorodeoxyglucose (18F-FDG) uptake. It is likely that the b-adrenergic pathway is responsible for the increased IBAT glucose uptake observed in the female offspring from the increase in phosphorylated GSK3b and uncoupling protein 1 (UCP1) protein expression. While non-significant, these measures account for only a single time point in the rodent lifespan. The results of this study indicate alterations in glucose uptake and metabolism are significant in mice at 4 months of age. These findings suggest that sub-lethal dose radiation alters glucose metabolism in the IBAT and liver of offspring and changes may progress with age.