The impact of exercise training on adipose tissue remodelling in cancer cachexia

Cachexia affects the majority of patients with advanced cancer and no effective treatment is currently available to address this paraneoplastic syndrome. It is characterized by a reduction in body weight due to the loss of white adipose tissue (WAT) and skeletal muscle. The loss of WAT seems to occur at an earlier time point than skeletal muscle proteolysis, with recent evidence suggesting that the browning of WAT may be a major contributor to this process. Several factors seem to modulate WAT browning including pro-inflammatory cytokines; however, the underlying molecular pathways are poorly characterized. Exercise training is currently recommended for the clinical management of low-grade inflammatory conditions as cancer cachexia. While it seems to counterbalance the impairment of skeletal muscle function and attenuate the loss of muscle mass, little is known regarding its effects in adipose tissue. The browning of WAT is one of the mechanisms through which exercise improves body composition in overweight/obese individuals. While this effect is obviously advantageous in this clinical setting, it remains to be clarified if exercise training could protect or exacerbate the cachexia-related catabolic phenotype occurring in adipose tissue of cancer patients. Herein, we overview the molecular players involved in adipose tissue remodelling in cancer cachexia and in exercise training and hypothesize on the mechanisms modulated by the synergetic effect of these conditions. A better understanding of how physical activity regulates body composition will certainly help in the development of successful multimodal therapeutic strategies for the clinical management of cancer cachexia.