Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, IL.
School of Human Kinetics, University of Ottawa, Ottawa, ON, CANADA.
Med Sci Sports Exerc. 2019 Jun;51(6):1126-1136. doi: 10.1249/MSS.0000000000001894.
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.
放射治疗的晚期效应会对长期癌症幸存者的健康和生活质量产生重大影响。放射诱导造血干细胞和祖细胞（HSPC）及其骨髓微环境的持久改变；然而，肥胖和运动等宿主因素如何在辐射暴露后差异调节 HSPC 含量及其骨髓微环境仍不清楚。本研究旨在评估肥胖和运动训练的组合如何在亚致死辐射暴露后调节小鼠的 HSPC 及其龛位。
肥胖诱导采用高脂饮食喂养的小鼠保持久坐或进行渐进式跑步机运动计划。在 13 周龄时，对小鼠进行辐照（3 Gy），并继续进行特定的饮食和运动计划四周。
运动训练的小鼠具有显著更高数量的几种 HSPC 亚群和骨髓基质细胞群，而肥胖小鼠的 HSPC 亚群在辐射后显著降低。运动训练显著降低了 HSPC 中的活性氧含量。骨髓上清液的蛋白质组学分析表明，运动训练的小鼠有生物学相关变化的聚类。骨髓上清液的功能评估显示，肥胖小鼠的白血病母细胞活力显著增加，但运动训练的小鼠没有（P < 0.05）。
这些数据表明，运动训练部分恢复了肥胖对辐射暴露后 HSPC 及其龛位的负面影响。因此，对于接受过放射治疗的肥胖或非肥胖癌症幸存者，应考虑运动训练来减轻放射治疗对造血系统的晚期影响。
