Cancer cachexia: effects of aerobic physical training on skeletal muscle in animal model

Abstract

Cancer is the leading cause of death in most developed countries and the second leading cause of death in developing countries. Approximately 80% of cancer patients in advanced stages have cachexia, which can be defined as a multifactorial syndrome characterized by loss of skeletal muscle mass (with or without loss of fat mass) that cannot be reversed by conventional nutritional support and results in progressive disability. Therefore, strategies to attenuate the atrophy and dysfunction of energy metabolism of skeletal muscle in cancer patients are necessary. Among the non-pharmacological strategies, we highlight the therapeutic role of moderate-intensity aerobic exercise training. Nevertheless, recent evidence suggests that the high-intensity interval exercise training is more effective than moderate-intensity aerobic exercise training to promote functional adaptations in skeletal muscle of subjects with chronic degenerative diseases. However, the effect of high-intensity interval exercise training upon skeletal muscle in experimental models of cancer cachexia still unexplored. Moreover, understanding the mechanisms involved in the possible attenuation of muscle atrophy and energy metabolism dysfunction on cancer cachexia is necessary. Therefore, the aim of this project is to evaluate the effects moderate-intensity aerobic exercise training and high-intensity interval exercise training on tropism and energy metabolism of skeletal muscle in mice with cancer cachexia. For this, this project will be divided into three studies. The first study began at the Master´s degree and it was the first step to enable this project, standardizing the experimental model Walker 256 in our laboratory. Whereas Walker 256 tumor can develop in different regions, we evaluated two regions for the inoculum of tumor cells (i.e. subcutaneous region and bone marrow), and based on these findings, we were able to determine the time course and choose the best region for the inoculum. The second study aims to evaluate the survival and tumor development by computed tomography in animals with cancer cachexia underwent to different exercise training protocols. Finally , the third study aim to answer the following questions: 1) Are moderate-intensity aerobic exercise training and high-intensity interval exercise training able to attenuate skeletal muscle dysfunction in rats with cancer cachexia? and 2) What are the main physiological mechanisms involved in cachexia and what are the effects of these two types of exercise training upon them? For this purpose, different methodological strategies will be implemented to evaluate the effects of aerobic exercise training on 1) the exercise tolerance and skeletal muscle function, 2) other indicators of cachexia, 3) pain tolerance, 4) morphological and functional parameters of the muscles plantaris and soleus , 5) energy metabolism of the plantaris and soleus, 6) the redox state of the plantaris and soleus and 7) the activation of components of ubiquitin proteasome system in plantaris and soleus. (AU)