Efficiency of oxidative phosphorylation in liver mitochondria is decreased in a rat model of peritoneal carcinosis

Background & Aims Cancer cachexia is a dynamic process characterized by a negative energy balance induced by anorexia and hypermetabolism. The mechanisms leading to hypermetabolism are not totally elucidated. This study examines the efficiency of oxidative phosphorylation and energy wasting in liver mitochondria isolated from rats with cancer cachexia induced by peritoneal carcinosis (PC). Methods PC was generated by an intraperitoneal injection of cancer cells (PROb) in BDIX rats. The efficiency of oxidative phosphorylation and energy wasting as well as the role played by reactive oxygen species (ROS) and cardiolipin (mitochondrial inner membrane phospholipid) in these processes were assessed in liver mitochondria of PC and pair-fed control rats. Results The efficiency of oxidative phosphorylation decreased (−26%) while energy wasting increased (+22%) in liver mitochondria from PC compared to control rats. The increased energy wasting was associated with a higher cardiolipin content (+55%, p<0.05; R2 = 0.64, p<0.05) and with a lower n−6/n−3 polyunsaturated fatty acid ratio in cardiolipin (−45%, p<0.05; R2 = 0.21, p<0.05) in PC rats. ROS production was increased by 12-fold in liver mitochondria from PC rats. Conclusions The efficiency of ATP synthesis was reduced and energy wasting processes were increased in liver mitochondria of PC rats. This suggests that liver mitochondria from PC rats request more nutrients than liver mitochondria from control rats to maintain the same ATP production. These alterations were associated to the content and fatty acid composition of cardiolipin. Cancer cachexia is a dynamic process characterized by a negative energy balance induced by anorexia and hypermetabolism. The mechanisms leading to hypermetabolism are not totally elucidated. This study examines the efficiency of oxidative phosphorylation and energy wasting in liver mitochondria isolated from rats with cancer cachexia induced by peritoneal carcinosis (PC). PC was generated by an intraperitoneal injection of cancer cells (PROb) in BDIX rats. The efficiency of oxidative phosphorylation and energy wasting as well as the role played by reactive oxygen species (ROS) and cardiolipin (mitochondrial inner membrane phospholipid) in these processes were assessed in liver mitochondria of PC and pair-fed control rats. The efficiency of oxidative phosphorylation decreased (−26%) while energy wasting increased (+22%) in liver mitochondria from PC compared to control rats. The increased energy wasting was associated with a higher cardiolipin content (+55%, p<0.05; R2 = 0.64, p<0.05) and with a lower n−6/n−3 polyunsaturated fatty acid ratio in cardiolipin (−45%, p<0.05; R2 = 0.21, p<0.05) in PC rats. ROS production was increased by 12-fold in liver mitochondria from PC rats. The efficiency of ATP synthesis was reduced and energy wasting processes were increased in liver mitochondria of PC rats. This suggests that liver mitochondria from PC rats request more nutrients than liver mitochondria from control rats to maintain the same ATP production. These alterations were associated to the content and fatty acid composition of cardiolipin.