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.

Keywords:

• Thoracic irradiation
• obesity
• mitochondria
• metabolic signaling
• mouse model

Disclosure statement

The authors have no conflicts of interest to declare.

Notes on contributors

Steven B. Zhang is a Research Assistant Professor. His studies have focused on animal and human medicine in clinical, translational, and basic sciences. He specializes in the effects of radiation on mitochondrial DNA and identifying novel biomarkers for radiation.

Shanmin Yang is a retired Research Assistant Professor. His work focused on discovering novel mitigation agents for radiation-induced pulmonary fibrosis. He has also explored the molecular biology of tumor metastasis and worked to discover new drugs that inhibit these metastases.

Zhenhuan Zhang is an Assistant Scientist. His research interest is in radiation-enhanced tumor suppression in breast cancer. Has has over 15 years of experience in medical research that has led me to publish over 40 peer-reviewed publications.

Amy Zhang is a Research Assistant who was trained to work with in vitro models for a variety of projects. She has mastered the necessary skills to independently run different experiments.

Mei Zhang is a specialist in gene expression & genotyping.

Liangjie Yin Yin is an Assistant-In.

Katherine Casey-Sawicki is a research coordinator and science editor with extensive experience working with ESL writers. She carries out the manuscript and publication process for the basic research and physics faculty, edits and assists with grants, and is a department administrator for tenure and promotion.

Steven Swarts is a Research Associate Professor. His specialties include analytic chemistry and screening active compounds for mitigation of radiation effects.

Sadasivan Vidyasagar is a Research Professor. He specializes in gastroenterology, electrophysiology, and mathematical modeling.

Lurong Zhang is an Adjunct Professor. She has explored several research areas since 1984, resulting in over 90 publications and 12 grants.

Paul Okunieff is Professor and Chair of the Department of Radiation Oncology. His research interests include stereotactic radiosurgery, oligometastases, translational research, and countermeasures research.

Additional information

Funding

This work was funded by National Institute of Allergy and Infectious Diseases (U19 AI067733-02 Okunieff (PI): 09/01/2005-08/31/2010).