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

被引：5

作者：

Davidson, Caitlund Q. ^{[1
]}

Tharmalingam, Sujeenthar ^{[2
]}

Niccoli, Sarah ^{[1
]}

Nemec-Bakk, Ashley ^{[1
]}

Khurana, Sandhya ^{[2
]}

Murray, Alyssa ^{[2
]}

Tai, T. C. ^{[2
]}

Boreham, Douglas R. ^{[2
,3
]}

Khaper, Neelam ^{[1
,4
]}

Lees, Simon J. ^{[1
,4
]}

机构：

[1] Lakehead Univ, Dept Biol, Thunder Bay, ON, Canada

[2] Laurentian Univ, Northern Ontario Sch Med, Div Med Sci, Sudbury, ON, Canada

[3] McMaster Univ, Dept Med Phys & Appl Radiat Sci, Hamilton, ON, Canada

[4] Lakehead Univ, Northern Ontario Sch Med, Div Med Sci, Thunder Bay, ON, Canada

来源：

PLOS ONE | 2020年 / 15卷 / 04期

基金：

加拿大自然科学与工程研究理事会;

关键词：

INSULIN-RESISTANCE; PHOSPHOENOLPYRUVATE CARBOXYKINASE; GLUCOCORTICOID EXPOSURE; LATE-GESTATION; GROWTH; MICE; SENSITIVITY; BEHAVIOR; OBESITY; SOCS-1;

D O I：

10.1371/journal.pone.0231650

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 F-18-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.

引用

页数：20