TY - JOUR
T1 - Adipose Triglyceride Lipase Contributes to Cancer-Associated Cachexia
AU - Das, Suman K.
AU - Eder, Sandra
AU - Schauer, Silvia
AU - Diwoky, Clemens
AU - Temmel, Hannes
AU - Gürtl, Barbara
AU - Gorkiewicz, Gregor
AU - Tamilarasan, Kuppusamy P.
AU - Kumari, Pooja
AU - Trauner, Michael
AU - Zimmermann, Robert
AU - Vesely, Paul
AU - Hämmerle, Günter
AU - Zechner, Rudolf
AU - Höfler, Gerald
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
UR - http://www.sciencemag.org/content/333/6039/233.abstract
UR - http://www.sciencemag.org/content/early/2011/06/15/science.1198973.abstract
U2 - 10.1126/science.1198973
DO - 10.1126/science.1198973
M3 - Article
SN - 1095-9203
VL - 333
SP - 233
EP - 238
JO - Science
JF - Science
IS - 6039
ER -
