Abstract
Exercise training is considered as a potential intervention to counteract muscle degeneration in cancer cachexia. However, evidence to support such intervention is equivocal. Therefore, we investigated the effect of exercise training, i.e. voluntary wheel running, on muscle wasting, functional capacity, fiber type composition and vascularization during experimental cancer cachexia in mice. Balb/c mice were injected with PBS (CON) or C26 colon carcinoma cells to induce cancer cachexia (C26). Mice had free access to a running wheel in their home cage (CONEX and C26EX, n = 8–9) or were sedentary (CONS and C26S, n = 8–9). Mice were sacrificed 18 days upon tumor cell injection. Immunohistochemical analyes were performed on m. gastrocnemius and quadriceps, and ex vivo contractile properties were assessed in m. soleus and extensor digitorum longus (EDL). Compared with CON, C26 mice exhibited body weight loss (~ 20 %), muscle atrophy (~ 25 %), reduced grip strength (~ 25 %), and lower twitch and tetanic force (~ 20 %) production in EDL but not in m. soleus. Furthermore, muscle of C26 mice were characterizd by a slow-to-fast fiber type shift (type IIx fibers: +57 %) and increased capillary density (~ 30 %). In C26 mice, wheel running affect neither body weight loss, nor muscle atrophy or functional capacity, nor inhibited tumor growth. However, wheel running induced a type IIb to type IIa fiber shift in m. quadriceps from both CON and C26, but not in m. gastrocnemius. Wheel running does not exacerbate muscular degeneration in cachexic mice, but, when voluntary, is insufficient to improve the muscle phenotype.
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The authors want to thank Monique Ramaekers for assistance during the study and assistance with sample collection and analysis.
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Conception and design of the study: CH and PH. Data collection and analysis: CH and SD. Analysis and interpretation of the data: CH, KK and PH. Manuscript drafting: SD, CH and PH.
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Hiroux, C., Dalle, S., Koppo, K. et al. Voluntary exercise does not improve muscular properties or functional capacity during C26-induced cancer cachexia in mice. J Muscle Res Cell Motil 42, 169–181 (2021). https://doi.org/10.1007/s10974-021-09599-6
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DOI: https://doi.org/10.1007/s10974-021-09599-6