Thoracic gamma irradiation-induced obesity in C57BL/6 female mice

Abstract

Purpose: To investigate the late effects of thoracic region irradiation (TRI) on mouse body weight. Materials and methods: Female C57BL/6 mice were divided into nonirradiated, 5 Gy total body irradiation, 9 Gy sub-total body irradiation, and 12.5 Gy thoracic region irradiation (TRI) groups. Changes in mouse weight were monitored every other week at similar time points for 12 months. The anatomical characteristics of abdominal visceral fat distribution were recorded, and mitochondrial DNA copy number in the hearts and livers and lipid metabolic signaling in the liver were analyzed. Data were analyzed by one-way analysis of variance and a student's t-test. Results: TRI led to a significant increase (p < .001) in body weight that was dependent on time and individuals [42.1% of mice were overweight (50% increase in body weight) 4 months post-TRI and 100% of mice were overweight at 10 months post-TRI]. Gross anatomical features of abdominal visceral fat distribution and storage in radiation-induced overweight/severely overweight mice were similar to those of high fat diet-induced overweight/severely overweight mice. The mitochondrial genome of heart and liver tissues from overweight/severely overweight mice had significantly (p < .05) decreased functional mitochondrial DNA copy number (ratios decreased from 1 to 0.71 or 0.49, respectively) and significantly (p < .05) increased mitochondrial DNA mutations (ratios increased from 1 to 3.21 or 1.83, respectively). CPT1 and IRS2 lipid metabolic signaling was significantly (p < .05-.01) decreased for both mRNA (fold decrease from 1 to 0.60 or 0.55, respectively) and protein (fold decrease from 1 to 0.62 or 0.19, respectively). Conclusions: TRI can cause mice to gain weight. These findings indicate that TRI can result in lipid metabolic abnormalities and provide a model to study the factors that result in these abnormalities. ARTICLE HISTORY

Complex Long-term Effects of Radiation on Adult Mouse Behavior

“…A significant effect of radiation on body weight gain in female mice was previously reported for doses of 3-12.5 Gy 49,50 , and our results extend them to lower doses and to male mice. Similar to our findings, the dose-response curve became inverse 3-4 months p.i.…”

Ionizing radiation promotes, whereas calorie restriction suppresses, NASH and hepatocellular carcinoma in mice

“…The mechanism by which radiation exposure induces NASH is unclear. Exposure of the thoracic region or liver to high doses of radiation (>10 Gy) reportedly induces obesity in female C57BL/6 mice 27 and short‐term (~48 hours) changes in liver fatty‐acid translocation/metabolism in rats, 28 although the mechanisms that have been proposed may not necessarily hold for our present long‐term study (~600 days) because those previous studies used high‐dose, partial‐body irradiation without long‐term observation. Our data show that the expression of many genes related to metabolic regulation was altered at an early stage (~100 days) after radiation exposure.…”