期刊
CELL METABOLISM
卷 20, 期 3, 页码 433-447出版社
CELL PRESS
DOI: 10.1016/j.cmet.2014.06.011
关键词
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资金
- Deutsche Forschungsgemeinschaft, Germany [SFB654]
- Paul Ainsworth and the Dawkins family
- Fondation Leducq [12CVD04]
- ERC [340896, ERC-FCK/2008/37]
- Austrian Science Fund
- Banco Bilbao Vizcaya Argentaria Foundation (F-BBVA) from the Spanish Ministry of Economy [BFU2012-40230]
- Caj-Navarra fellowship
- Union for International Cancer Control
- Austrian Science Fund (FWF) [F 3002, Z 136] Funding Source: researchfish
- European Research Council (ERC) [340896] Funding Source: European Research Council (ERC)
Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice. Chronic inflammation and the cytokine interleukin-6 increase UCP1 expression in WAT, and treatments that reduce inflammation or beta-adrenergic blockade reduce WAT browning and ameliorate the severity of cachexia. Importantly, UCP1 staining is observed in WAT from CAC patients. Thus, inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients.
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