Low‐Intensity Exercise Protects Skeletal and Cardiac Muscle Against Cancer‐Mediated Muscle Wasting via Regulation of Autophagy and Inflammation

ABSTRACT Background Up to 80% of cancer patients suffer from skeletal and cardiac muscle wasting, also known as cancer cachexia. This metabolic wasting syndrome is responsible for up to one‐third of deaths in these cancer patients. Treatment options to attenuate muscle loss are limited. However, research shows that exercise interventions can slow tumour development and preserve muscle mass and function. Questions remain regarding the most effective modalities of exercise as a preventative intervention against cancer‐mediated muscle wasting. The purpose of this study was to determine if low‐intensity treadmill exercise can act as a protective measure and intervention against cancer‐mediated muscle wasting in male mice. Methods Male LC3 Tg+ and WT mice were randomly separated into four groups: sedentary non‐tumour bearing (SED + NT), sedentary tumour bearing (SED + T), low‐intensity treadmill exercise non‐tumour bearing (TM + NT) and low‐intensity treadmill exercise tumour bearing (TM + T). Mice were implanted with tumour cells (T group; 5 × 10 5 LLC cells in flank) or remained non‐tumour (NT) for 4 weeks. During the 4 weeks, mice underwent a low‐intensity treadmill training protocol (TM) or remained sedentary (SED). Grip strength, echocardiography and tumour growth was assessed, and inflammatory and autophagic protein pathways in skeletal and cardiac muscle tissue were investigated. Results SED + T mice exhibited worst grip strength and cardiac function (fractional shortening). Coinciding with worse skeletal and cardiac function, inflammatory and autophagic pathways were abnormally upregulated in SED + T mice compared with NT controls ( p < 0.05). Low‐intensity exercise protected musculature by cardiac function and grip strength in TM + T compared with SED + T mice. Low‐intensity exercise attenuated inflammation and autophagy in TM + T mice. Additionally, treadmill exercise resulted in significantly smaller tumour mass and volume ( p < 0.05) in the TM + T compared with SED + T group. Conclusions Our data indicated cardioprotective, myoprotective and tumour‐suppressive effects of low‐intensity treadmill exercise in tumour bearing mice. Low‐intensity exercise preserved skeletal and cardiac muscle function and inhibited tumour growth by regulating autophagy and inflammation. Therefore, low‐intensity treadmill exercise may be an effective, affordable and accessible adjuvant treatment for cancer patients.