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 and progenitor cells (HSPC) and the bone marrow environment; however, how relevant host factors such as obesity and exercise differentially regulate HSPC content and the bone marrow environment after radiation exposure remains unknown. The purpose of this investigation was to evaluate how the combination of obesity and exercise training modulates HSPC and their niche after sublethal radiation exposure in mice.
Mice fed either a control or a high-fat diet to induce obesity remained sedentary or underwent a progressive treadmill exercise program. At 13 wk of age, mice were irradiated (3 Gy) and continued their specific diets and exercise program for four more weeks.
Exercise-trained mice had significantly higher quantities of several HSPC subpopulations and bone marrow stromal cell populations, whereas HSPC subpopulations were significantly lower in obese mice after radiation. Reactive oxygen species content was significantly decreased in HSPC 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 < 0.05).
Together, these data suggest that exercise training partially restores the negative effects of obesity on HSPC and their niche after radiation exposure. As such, exercise training should be considered to mitigate the late effects of radiation therapy on the hematopoietic system for cancer survivors with or without obesity who have undergone radiation therapy.
1Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, IL;
2School of Human Kinetics, University of Ottawa, Ottawa, ON, CANADA;
3Department of Food Sciences and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL;
4Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Champaign, IL; and
5Regenerative Medicine Program, Centre on Neuromuscular Disease, and Brain and Mind Institute, University of Ottawa, Ottawa, ON, CANADA
Address for correspondence: Michael De Lisio, Ph.D., Roger Guindon Hall, University of Ottawa, 451 Smyth Rd., Ottawa, ON, Canada K1H 8L1; E-mail: firstname.lastname@example.org.
Submitted for publication August 2018.
Accepted for publication January 2019.