Voluntary exercise reduces cachexia and improves muscle function in mice carrying mammary gland tumors

Abstract

Cachexia is a common feature in patients suffering from cancer. Here we use a PyMT knock in mice that develops spontaneous mammary gland tumors to study the effect of voluntary wheel running on skeletal muscle function. Mice were housed with the possibility to engage in voluntary exercise by a running wheel in the cage. Controls were housed with an immovable running wheel. Force at different frequencies and force during fatigue and recover was measured in isolated soleus (Slow twitch) and extensor digitorum longus (fast twitch).In controls, soleus presented with clear atrophy in tumor carrying mice (6.7±0.5vs. 8.0±0.6 mg) and force at 100 Hz was reduced (51.4±5.6 vs. 88.8±16.5 kPa). Mice that exercised had a tendency for increased muscle mass (7.0±0.4 mg) and a compensated muscle force at 100Hz compared to voluntary run wild types (118.3±16.6kPa vs. 117.1±17.0kPa).Western blot of whole muscle indicate that tumor mice had ~30% less PGC‐1α in both Soleus and EDL where a small increase could be seen in tumor carrying mice that had been running.ConclusionSkeletal muscles are afflicted by system wide influence from tumor growth. This effect can however to some extent be prevented by engaging in regular exercise.