Publication Date:
2011-06-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- F 3001/Austrian Science Fund FWF/Austria -- F 3002/Austrian Science Fund FWF/Austria -- F 3013/Austrian Science Fund FWF/Austria -- Z 136/Austrian Science Fund FWF/Austria -- New York, N.Y. -- Science. 2011 Jul 8;333(6039):233-8. doi: 10.1126/science.1198973. Epub 2011 Jun 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Pathology, Medical University of Graz, Graz, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21680814" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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