A metabolic change towards fermentation drives cancer cachexia in myotubes

The findings reported in this thesis hihlight the pivotal role of a metabolic change towards fermentation in the induction of cancer cachexia in myotubes treated with the conditioned medium of CT26 murine colon carcinoma cell line. Particularly, cachectic myotubes manifest a reduced oxygen consumption, increased lactate production and several mitochondrial alterations including a decreased activity of PDH. Our results reveal that PDH activity restoration, achieved by glycolysis or lactic fermentation inhibition was able to prevent cancer cachexia induction and previously observed metabolic alterations. This could be due to an increased availability of pyruvate within mitochondria. In agreement, pyruvate supplementation was able to prevent cancer cachexia induction and previously observed metabolic alterations, triggering a PDH activity restoration. Thus, pyruvate supplementation could represent a new tool to counteract cancer cachexia induction and development.