Adipose Triglyceride Lipase Contributes to Cancer-Associated Cachexia

• Published in: Science (American Association for the Advancement of Science) 2011-07, Vol.333 (6039), p.233-238
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Ablation; Adipose Tissue, White - enzymology; Adipose Tissue, White - pathology; Adipose tissues; Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Blood Glucose - metabolism; Body fat; Body Mass Index; Body Weight; Cachexia; Cachexia - enzymology; Cachexia - etiology; Cachexia - pathology; Cancer; Cytokines - blood; Experimental tumors, general aspects; Fatty Acids - blood; Genetics; Glycerol - metabolism; Humans; Inhibition; Lipase; Lipase - deficiency; Lipase - genetics; Lipase - metabolism; Lipids; Lipolysis; Mass; Medical disorders; Medical sciences; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Muscle, Skeletal - pathology; Muscles; Myocardium - pathology; Neoplasms - complications; Neoplasms - enzymology; Neoplasms - pathology; Neoplasms, Experimental - complications; Neoplasms, Experimental - enzymology; Neoplasms, Experimental - pathology; Pathogenesis; Peptides - metabolism; Sterol Esterase - deficiency; Sterol Esterase - genetics; Sterol Esterase - metabolism; Triglycerides; Triglycerides - blood; Tumors; Weight Loss; White adipose tissue
• ISSN: 0036-8075; 1095-9203
• 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.