Effects of Obesity and Exercise on Bone Marrow Progenitor Cells following Radiation

INTRODUCTION The late effects of radiation therapy can have significant consequences for the health and quality of life of long-term cancer survivors. Radiation induces persistent alterations in hematopoietic stem/progenitor cells (HSPCs) and the bone marrow environment; however, how relevant host factors such as obesity and exercise differentially regulate HSPC content and the bone marrow environment following radiation exposure remains unknown. The purpose of this investigation was to evaluate how the combination of obesity and exercise training modulate HSPCs and their niche following sub-lethal radiation exposure in mice. METHODS Mice fed either a control or high-fat-diet to induce obesity remained sedentary or underwent a progressive treadmill exercise program. At 13 weeks of age, mice were irradiated (3 Gy), and continued their specific diets and exercise program for four more weeks. RESULTS Exercise trained mice had significantly higher quantities of several HSPC subpopulations and bone marrow stromal cell populations, while HSPC subpopulations were significantly lower in obese mice following radiation. Reactive oxygen species content was significantly decreased in HSPCs with exercise training. Proteomics analysis of bone marrow supernatant revealed clustering of biologically relevant changes in exercise trained mice. Functional evaluation of bone marrow supernatant revealed a significant increase in leukemia blast viability in obese mice but not in the exercise trained mice (p

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