Adipose Triglyceride Lipase Contributes to Cancer-Associated Cachexia

作者：Das Suman K; Eder Sandra; Schauer Silvia; Diwoky Clemens; Temmel Hannes; Guertl Barbara; Gorkiewicz Gregor; Tamilarasan Kuppusamy P; Kumari Pooja; Trauner Michael; Zimmermann Robert; Vesely Paul; Haemmerle Guenter; Zechner Rudolf^*; Hoefler Gerald

来源：Science, 2011, 333(6039): 233-238.

DOI：10.1126/science.1198973

Cachexia is a multifactorial wasting syndrome most common in patients with cancer that is characterized by the uncontrolled loss of adipose and muscle mass. We show that the inhibition of lipolysis through genetic ablation of adipose triglyceride lipase (Atgl) or hormone-sensitive lipase (Hsl) ameliorates certain features of cancer-associated cachexia (CAC). In wild-type C57BL/6 mice, the injection of Lewis lung carcinoma or B16 melanoma cells causes tumor growth, loss of white adipose tissue (WAT), and a marked reduction of gastrocnemius muscle. In contrast, Atgl-deficient mice with tumors resisted increased WAT lipolysis, myocyte apoptosis, and proteasomal muscle degradation and maintained normal adipose and gastrocnemius muscle mass. Hsl-deficient mice with tumors were also protected although to a lesser degree. Thus, functional lipolysis is essential in the pathogenesis of CAC. Pharmacological inhibition of metabolic lipases may help prevent cachexia.

• 出版日期2011-7-8
• 单位河北医科大学