Adipose triglyceride lipase contributes to cancer-associated cachexia.

Abstract

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.

• Authors: Suman K Das, Sandra Eder, Silvia Schauer, Clemens Diwoky, Hannes Temmel, Barbara Guertl, Gregor Gorkiewicz, Kuppusamy P Tamilarasan, Pooja Kumari, Michael Trauner, Robert Zimmermann, Paul Vesely, Guenter Haemmerle, Rudolf Zechner, Gerald Hoefler
• Journal: Science (New York, N.Y.) (Science) Vol. 333 Issue 6039 Pg. 233-8 (Jul 08 2011) ISSN: 1095-9203 [Electronic] United States
• PMID: 21680814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Cytokines
• Fatty Acids
• Peptides
• Triglycerides
• lipid mobilizing substance
• Sterol Esterase
• Lipase
• Glycerol

Topics

• Adipose Tissue, White (enzymology, pathology)
• Animals
• Blood Glucose (metabolism)
• Body Mass Index
• Body Weight
• Cachexia (enzymology, etiology, pathology)
• Cytokines (blood)
• Fatty Acids (blood)
• Glycerol (metabolism)
• Humans
• Lipase (deficiency, genetics, metabolism)
• Lipolysis
• Melanoma, Experimental
• Mice
• Mice, Inbred C57BL
• Muscle, Skeletal (pathology)
• Myocardium (pathology)
• Neoplasms (complications, enzymology, pathology)
• Neoplasms, Experimental (complications, enzymology, pathology)
• Peptides (metabolism)
• Sterol Esterase (deficiency, genetics, metabolism)
• Triglycerides (blood)
• Weight Loss