Journal of Cachexia, Sarcopenia and Muscle (JCSM) - Abstract


 Volume 3, Number 4, Page 265 - 275

Cancer cachexia is associated with a decrease in skeletal muscle mitochondrial oxidative capacities without alteration of ATP production efficiency

Cloé M. Julienne, Jean-François Dumas, Caroline Goupille, Michelle Pinault, Cécile Berri, Anne Collin, Sophie Tesseraud, Charles Couet and Stephane Servais

Background  
Cancer cachexia is a complex syndrome related to a negative energy balance resulting in muscle wasting. Implication of muscle mitochondrial bioenergetics alterations during cancer cachexia was suggested. Therefore, the aim of this study was to explore the efficiency of oxidative phosphorylation in skeletal muscle mitochondria in a preclinical model of cancer cachexia.
Methods  
Berlin–Druckrey IX rats with peritoneal carcinosis (PC) were used as a model of cancer cachexia with healthy pair-fed rats (PF) as control. Hindlimb muscle morphology and fibre type composition were analysed in parallel with ubiquitin ligases and UCP gene expression. Oxidative phosphorylation was investigated in isolated muscle mitochondria by measuring oxygen consumption and ATP synthesis rate.
Results  
PC rats underwent significant muscle wasting affecting fast glycolytic muscles due to a reduction in fibre cross-sectional area. MuRF1 and MAFbx gene expression were significantly increased (9- and 3.5-fold, respectively) in the muscle of PC compared to PF rats. Oxygen consumption in non-phosphorylating state and the ATP/O were similar in both groups. Muscle UCP2 gene was overexpressed in PC rats. State III and the uncoupled state were significantly lower in muscle mitochondria from PC rats with a parallel reduction in complex IV activity (−30 %).
Conclusion  
This study demonstrated that there was neither alteration in ATP synthesis efficiency nor mitochondrial uncoupling in skeletal muscle of cachectic rats despite UCP2 gene overexpression. Muscle mitochondrial oxidative capacities were reduced due to a decrease in complex IV activity. This mitochondrial bioenergetics alteration could participate to insulin resistance, lipid droplet accumulation and lactate production

Julienne C.M., Dumas J.F., Goupille C., Pinault M., Berri C., Collin A., Tesseraud S., Couet C., Servais S., Cancer cachexia is associated with a decrease in skeletal muscle mitochondrial oxidative capacities without alteration of ATP production efficiency
J Cachex Sarcopenia Muscle 2012;4:265-275