Weight loss with exercise improves muscle architecture and progenitor cell populations compared with weight loss alone in mice with preneoplastic colorectal lesions.

Weight loss and exercise reduce colorectal cancer (CRC) risk in persons with obesity. Whether weight loss and exercise effect myofiber characteristics and muscle stem/progenitor cell populations in mice with preneoplastic colorectal lesions, a model of CRC risk, is unknown. To address this gap, male C57Bl/6J mice were fed a high-fat diet (HFD) to induce obesity or a control (CON) diet prior to azoxymethane injection to induce preneoplastic colorectal lesions. The HFD group was then randomized to weight loss conditions that included (1) switching to the CON diet only (HFD-SED) or switching to the CON diet with treadmill exercise training (HFD-EX). Average myofiber cross-sectional area was not different between groups. There were more smaller-sized fibres in HFD-EX (p < 0.05 vs. CON), and more fibrosis in HFD-SED (p < 0.05 vs. HFD-EX and CON). There was a trend for more committed (Pax7+MyoD+) myoblasts (p = 0.059) and more fibro-adipogenic progenitors in HFD-EX (p < 0.05 vs. CON). Additionally, the canonical pro-inflammatory marker p-NF-κB was markedly reduced in the interstitium of HFD-EX (p < 0.05 vs. CON and HFD-SED). Our findings suggest that in mice with preneoplastic colorectal lesions, HFD followed by weight loss with exercise reduces muscle fibrosis and results in a higher content of muscle stem/progenitor cells. Novelty: Exercise improves muscle architecture in mice with preneoplastic colorectal lesion Exercise increases fibro/adipogenic progenitors and reduces inflammatory signaling in mice with preneoplastic colorectal lesions.

The Late Effects of Radiation Therapy on Skeletal Muscle Morphology and Progenitor Cell Content are Influenced by Diet-Induced Obesity and Exercise Training in Male Mice.

Radiation exposure during muscle development induces long-term decrements to skeletal muscle health, which contribute to reduced quality of life in childhood cancer survivors. Whether the effects of radiation on skeletal muscle are influenced by relevant physiological factors, such as obesity and exercise training remains unknown. Using skeletal muscle from our previously published work examining the effects of obesity and exercise training on radiation-exposed bone marrow, we evaluated the influence of these physiological host factors on irradiated skeletal muscle morphology and cellular dynamics. Mice were divided into control and high fat diet groups with or without exercise training. All mice were then exposed to radiation and continued in their intervention group for an additional 4 weeks. Diet-induced obesity resulted in increased muscle fibrosis, while obesity and exercise training both increased muscle adiposity. Exercise training enhanced myofibre cross-sectional area and the number of satellite cells committed to the myogenic lineage. High fat groups demonstrated an increase in p-NFĸB expression, a trend for a decline in IL-6, and increase in TGFB1. These findings suggest exercise training improves muscle morphology and satellite cell dynamics compared to diet-induced obesity in irradiated muscle, and have implications for exercise interventions in cancer survivors.