Increase in Muscle Mitochondrial Biogenesis Does Not Prevent Muscle Loss but Increased Tumor Size in a Mouse Model of Acute Cancer-Induced Cachexia

The Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
PLoS ONE (Impact Factor: 3.23). 03/2012; 7(3):e33426. DOI: 10.1371/journal.pone.0033426
Source: PubMed


Cancer-associated cachexia is a complex metabolic condition characterized by the progressive loss of body fat and deterioration of muscle mass. Although the cellular and molecular mechanisms of cachexia are incompletely understood, previous studies have suggested mitochondrial dysfunction in murine models of cancer cachexia. To better understand the metabolic shift in cancer-induced cachexia, we studied the effects of enhanced oxidative capacity on muscle wasting using transgenic mice over-expressing Peroxisome Proliferator-Activated Receptor gamma Co-activator-1α (PGC-1α) in skeletal muscle in a Lewis lung carcinoma-implanted model. Increased mitochondrial biogenesis was observed in the skeletal muscle of tumor-implanted mice. However, these increases did not prevent or reverse muscle wasting in mice harboring tumors. Moreover, tumor size was increased in muscle PGC-1α over-expressing mice. We found similar levels of circulating inflammatory cytokines in tumor-implanted animals, which was not affected by increased muscle expression of PGC-1α. Our data indicated that increased mitochondrial biogenesis in skeletal muscle is not sufficient to rescue tumor-associated, acute muscle loss, and could promote tumor growth, possibly through the release of myokines.

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    • "MCK-PGC-1α transgenic mice) [57] do not prevent skeletal muscle loss after Lewis lung tumor cell injection. Surprisingly, MCK-PGC-1α transgenic mice also led to the development of larger tumors [94]. Therefore, further experiments are absolutely necessary in order to elucidate the potential therapeutic effect of increased mitochondrial biogenesis in different models of cancer cachexia. "
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