Cachexia is a devastating form of muscle wasting that is commonly associated with cancer. To understand the molecular basis of cachexia-associated muscle atrophy, Fukawa et al. carried out transcriptomic- and metabolomic-profiling analysis of human muscle stem cell-based models and human cancer-induced cachexia models in mice. This analysis revealed that cachectic cancer cells secrete inflammatory factors that induce muscle fatty acid oxidation (FAO), leading to oxidative stress, p38 mitogen-activated protein kinase (MAPK) activation and progressive muscle wasting. Inhibition of fatty acid-induced oxidative stress using etomoxir rescued weight loss and improved muscle mass in cachectic mouse models.
References
Fukawa, T. et al. Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia. Nat. Med. http://dx.doi.org/10.1038/nm.4093 (2016)
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Crunkhorn, S. Inhibiting FAO rescues muscle-wasting. Nat Rev Drug Discov 15, 384 (2016). https://doi.org/10.1038/nrd.2016.101
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DOI: https://doi.org/10.1038/nrd.2016.101