fetal programming from sub-lethal radiation: glucose metabolism in the liver and brown adipose tissue
abstract
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.