Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/81480
Title: Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia
Authors: Fukawa, Tomoya
Ong, Pauline
Li, Zhimei
Chen, Shuwen
Mak, Shi Ya
Kanayama, Hiro-omi
Mohan, Rosmin Elsa
Wang, Ruiqi Rachel
Chua, Benjamin Yan-Jiang
Chua, Jason Min-Wen
Tan, Elwin Jun-Hao
Huang, Dan
Qian, Chao-Nan
Lim, Wan Jun
Lai, Jiunn Herng
Chua, Clarinda
Ong, Hock Soo
Tan, Ker-Kan
Ho, Ying Swan
Tan, Iain Beehuat
Teh, Bin Tean
Ng, Shyh-Chang
Keywords: Metabolic disorders
Cancer models
Issue Date: 2016
Source: Fukawa, T., Chua, B. Y.-J., Chua, J. M.-W., Tan, E. J.-H., Huang, D., Qian, C.-N., et al. (2016). Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia. Nature Medicine, 22(6), 666-671.
Series/Report no.: Nature Medicine
Abstract: Cachexia is a devastating muscle-wasting syndrome that occurs in patients who have chronic diseases. It is most commonly observed in individuals with advanced cancer1, 2, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer3, 4, 5. Additionally, although many people with cachexia show hypermetabolism3, 6, the causative role of metabolism in muscle atrophy has been unclear. To understand the molecular basis of cachexia-associated muscle atrophy, it is necessary to develop accurate models of the condition. By using transcriptomics and cytokine profiling of human muscle stem cell–based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors that rapidly led to high levels of fatty acid metabolism and to the activation of a p38 stress-response signature in skeletal muscles, before manifestation of cachectic muscle atrophy occurred. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, which leads to oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fatty acid–induced oxidative stress could be targeted to prevent cancer-induced cachexia.
URI: https://hdl.handle.net/10356/81480
http://hdl.handle.net/10220/42251
ISSN: 1078-8956
DOI: 10.1038/nm.4093
Rights: © 2016 Nature America, Inc.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:MAE Journal Articles

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