Adipose Triglyceride Lipase Contributes to Cancer-Associated Cachexia

被引：484

作者：

Das, Suman K. ^{[2
]}

Eder, Sandra ^{[1
]}

Schauer, Silvia ^{[2
]}

Diwoky, Clemens ^{[3
]}

Temmel, Hannes ^{[2
]}

Guertl, Barbara ^{[2
]}

Gorkiewicz, Gregor ^{[2
]}

Tamilarasan, Kuppusamy P. ^{[2
]}

Kumari, Pooja ^{[2
,4
]}

Trauner, Michael ^{[4
]}

Zimmermann, Robert ^{[1
]}

Vesely, Paul ^{[2
]}

Haemmerle, Guenter ^{[1
]}

Zechner, Rudolf ^{[1
]}

Hoefler, Gerald ^{[2
]}

机构：

[1] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

[2] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria

[3] Graz Univ Technol, Inst Med Engn, A-8010 Graz, Austria

[4] Med Univ Graz, Div Gastroenterol & Hepatol, Dept Internal Med, A-8036 Graz, Austria

来源：

SCIENCE | 2011年 / 333卷 / 6039期

基金：

奥地利科学基金会;

关键词：

WHOLE-BODY LIPOLYSIS; ENERGY-METABOLISM; SKELETAL-MUSCLE; WEIGHT-LOSS; FATTY-ACID; MICE; TISSUE; INFLAMMATION; DEFINITION; MECHANISMS;

D O I：

10.1126/science.1198973

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：233 / 238

页数：6

共 30 条

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