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

Abstract

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 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. Methods 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. Results 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). Conclusion 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.

Modulation of TRIB3 and Macrophage Phenotype to Attenuate Insulin Resistance After Downhill Running in Mice

“…Although it has been well accepted that exercise training is an effective method for treatment of IR induced by HFD-associated obesity, the clear mechanism by which exercise training attenuates adipose tissue inflammation to attenuate IR remains to be elucidated ( Macpherson et al, 2015 ; Emmons et al, 2019 ; Luo et al, 2020 ). Given the decreases of inflammation in downhill running and dietary regulation-treated mice, we further interested if exercise training and dietary regulation present similar effects on macrophages ( Luo et al, 2020 ).…”

Exercise training as prophylactic strategy in the management of neutropenia during chemotherapy

“…Observations in exercise trials on the incidence/duration of neutropenia and related criteria Emmons et al, 2019;Marędziak, Śmieszek, Chrząstek, Basinska, & Marycz, 2015). Furthermore, the proliferative capacity of stem and progenitor cells in the bone marrow was increased in voluntary lifelong exercising rats compared to sedentary controls (Stelzer et al, 2010).…”

The Potential of Physical Exercise to Mitigate Radiation Damage—A Systematic Review

“…Additionally, studies presenting inflammatory markers when exposed to radiation found that IL-1, IL-6, TNF-α, and TGF-β levels decreased in the intervention group that exercised. Emmons et al ( 27 ) also reported that progressive treadmill exercise in mice before exposure to γ-rays decreased bone marrow ROS levels (effect size 0.75). Studies reporting DNA damage with respect to micro-nucleation, Caspase 3/7 activity, and γH2AX foci indicating DNA DSBs all favored the intervention group with effect sizes ranging from 0.65 to 1.10 ( Figure 3 ) ( 27 , 37 – 42 ).…”

“…Cellular and tissue function outcomes were assessed with whole-body irradiations only, but showed effect sizes in favor of aerobic exercise with regard to bone marrow cellularity, reticulocytosis, metabolic enzyme activity, and bone mineralization/density ( 27 , 37 , 38 , 54 ). Emmons et al ( 27 ) reported that exercised mice had increased bone marrow cellularity, decreased marrow adipose tissue, and increased Lin − Sca-1 + c-kit + (LSK) cell populations as a response to exercise suggesting rescue of hematopoietic stem cells that were destructed by γ-irradiation, with effect sizes ranging from 0.81 to 1.49. Increased reticulocytosis and metabolic enzyme activity was observed when mice progressively exercised for 10 weeks after exposure to γ-rays compared to control ( 37 , 38 ).…”

“…Thus, as exercise initiates acute transient oxidative stress states that lead to protective long-term anti-inflammatory and other potential molecular radio-protective effects, these beneficial adaptive mechanisms induced by exercise could also potentially counteract the negative effects of IR exposure. Furthermore, similar benefits may have important implications for terrestrial medicine including cancer therapy and radiation protection ( 27 , 28 ).…”