title: 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.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Suman K
authors.initials: SK
authors.lastname: Das
authors.forename: Sandra
authors.initials: S
authors.lastname: Eder
authors.forename: Silvia
authors.initials: S
authors.lastname: Schauer
authors.forename: Clemens
authors.initials: C
authors.lastname: Diwoky
authors.forename: Hannes
authors.initials: H
authors.lastname: Temmel
authors.forename: Barbara
authors.initials: B
authors.lastname: Guertl
authors.forename: Gregor
authors.initials: G
authors.lastname: Gorkiewicz
authors.forename: Kuppusamy P
authors.initials: KP
authors.lastname: Tamilarasan
authors.forename: Pooja
authors.initials: P
authors.lastname: Kumari
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Paul
authors.initials: P
authors.lastname: Vesely
authors.forename: Guenter
authors.initials: G
authors.lastname: Haemmerle
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
mesh_terms: D052436:Adipose Tissue, White / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D002100:Cachexia / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005227:Fatty Acids / Q000097:blood; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D008049:Lipase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009369:Neoplasms / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D002787:Sterol Esterase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D005227:Fatty Acids; D010455:Peptides; D014280:Triglycerides; C008287:lipid mobilizing substance; D002787:Sterol Esterase; D008049:Lipase; D005990:Glycerol