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Dose threshold for radiation induced fetal programming in a mouse model at 4 months of age: Hepatic expression of genes and proteins involved in glucose metabolism and glucose uptake in brown adipose tissue.
- Source :
-
PloS one [PLoS One] 2020 Apr 21; Vol. 15 (4), pp. e0231650. Date of Electronic Publication: 2020 Apr 21 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Exposure to ionizing radiation contributing to negative health outcomes is a widespread concern. However, the impact of low dose and sub-lethal dose radiation (SLDR) exposures remain 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. To assess changes in gene expression profiles of glucose/insulin signaling and lipid metabolism caused by radiation exposure in utero, pregnant C57Bl/6J mice were irradiated using a dose response ranging from low dose to SLDR and compared to a Sham-irradiated group. mRNA expression analysis in 16 week old offspring (n = 84) revealed that genes involved in metabolic function including glucose metabolism, insulin signaling and lipid metabolism were unaffected by prenatal radiation exposures up to 300 mGy. However, female offspring of dams exposed to 1000 mGy had upregulated expression of genes contributing to insulin resistance and gluconeogenesis. In a second cohort of mice, the effects of SLDR on fetal programming of hepatic SOCS3 and PEPCK protein expression were assessed. 4 month old female offspring of dams irradiated at 1000 mGy had: 1) increased liver weights, 2) increased hepatic expression of proteins involved in glucose metabolism and 3) increased 18F-fluorodeoxyglucose (FDG) uptake in interscapular brown adipose tissue (IBAT) measured by positron emission tomography (PET) (n = 25). The results of this study indicate that prenatal radiation exposure does not affect metabolic function up to 300 mGy and 1000 mGy may be a threshold dose for sex-specific alterations in glucose uptake and hepatic gene and protein expression of SOCS3, PEPCK, PPARGC1A and PPARGC1B. These findings suggest that SLDR doses alter glucose uptake in IBAT and hepatic gene and protein expression of offspring and these changes may progress with age.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Adipose Tissue, Brown radiation effects
Animals
Blood Glucose metabolism
Carbohydrate Metabolism genetics
Disease Models, Animal
Fatty Liver genetics
Fatty Liver metabolism
Fatty Liver physiopathology
Female
Fetal Development radiation effects
Fetus
Glucose metabolism
Humans
Insulin metabolism
Lipid Metabolism genetics
Lipid Metabolism radiation effects
Liver pathology
Male
Mice
Pregnancy
Prenatal Exposure Delayed Effects
Radiation
Adipose Tissue, Brown growth & development
Fetal Development genetics
Insulin Resistance genetics
Liver metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 15
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 32315370
- Full Text :
- https://doi.org/10.1371/journal.pone.0231650