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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Das, SK; Eder, S; Schauer, S; Diwoky, C; Temmel, H; Guertl, B; Gorkiewicz, G; Tamilarasan, KP; Kumari, P; Trauner, M; Zimmermann, R; Vesely, P; Haemmerle, G; Zechner, R; Hoefler, G.
Adipose triglyceride lipase contributes to cancer-associated cachexia.
Science. 2011; 333(6039):233-238
Doi: 10.1126/science.1198973
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- Führende Autor*innen der Med Uni Graz
- Das Suman Kumar
- Höfler Gerald
- Co-Autor*innen der Med Uni Graz
- Diwoky Clemens
- Gorkiewicz Gregor
- Gürtl-Lackner Barbara
- Jha Pooja
- Kuppusamy Palaniappan Tamilarasan
- Schauer Silvia
- Trauner Michael
- Vesely Paul
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adipose Tissue, White - enzymology Adipose Tissue, White - pathology
- Animals -
- Blood Glucose - metabolism
- Body Mass Index -
- Body Weight -
- Cachexia - enzymology Cachexia - etiology Cachexia - pathology
- Cytokines - blood
- Fatty Acids - blood
- Glycerol - metabolism
- Humans -
- Lipase - deficiency Lipase - genetics Lipase - metabolism
- Lipolysis -
- Melanoma, Experimental -
- Mice -
- Mice, Inbred C57BL -
- Muscle, Skeletal - pathology
- Myocardium - pathology
- Neoplasms - complications Neoplasms - enzymology Neoplasms - pathology
- Neoplasms, Experimental - complications Neoplasms, Experimental - enzymology Neoplasms, Experimental - pathology
- Peptides - metabolism
- Sterol Esterase - deficiency Sterol Esterase - genetics Sterol Esterase - metabolism
- Triglycerides - blood
- Weight Loss -