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

Journal of Cachexia, Sarcopenia and Muscle

Julienne Cloé M.²  Dumas Jean-François²  Goupille Caroline²  Pinault Michelle²  Berri Cécile¹  Collin Anne¹  Tesseraud Sophie¹  Couet Charles² 

[1] INRA, Nouzilly;INSERM U921, Nutrition, Croissance et Cancer, Tours

关键词: Muscle atrophy;    PROb-BDIX model;    Energy wasting;    Cardiolipin;    UCP;    COX IV;   

DOI  :  10.1007/s13539-012-0071-9

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY-NC   
© 2012 The Authors. Published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.