title: Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism.
abstract: The mobilization of free fatty acids from adipose triacylglycerol (TG) stores requires the activities of triacylglycerol lipases. In this study, we demonstrate that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the major enzymes contributing to TG breakdown in in vitro assays and in organ cultures of murine white adipose tissue (WAT). To differentiate between ATGL- and HSL-specific activities in cytosolic preparations of WAT and to determine the relative contribution of these TG hydrolases to the lipolytic catabolism of fat, mutant mouse models lacking ATGL or HSL and a mono-specific, small molecule inhibitor for HSL (76-0079) were used. We show that 76-0079 had no effect on TG catabolism in HSL-deficient WAT but, in contrast, essentially abolished free fatty acid mobilization in ATGL-deficient fat. CGI-58, a recently identified coactivator of ATGL, stimulates TG hydrolase activity in wild-type and HSL-deficient WAT but not in ATGL-deficient WAT, suggesting that ATGL is the sole target for CGI-58-mediated activation of adipose lipolysis. Together, ATGL and HSL are responsible for more than 95% of the TG hydrolase activity present in murine WAT. Additional known or unknown lipases appear to play only a quantitatively minor role in fat cell lipolysis.
authors.affiliation: Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Schweiger
authors.forename: Renate
authors.initials: R
authors.lastname: Schreiber
authors.forename: Guenter
authors.initials: G
authors.lastname: Haemmerle
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
authors.forename: Christian
authors.initials: C
authors.lastname: Fledelius
authors.forename: Poul
authors.initials: P
authors.lastname: Jacobsen
authors.forename: Hans
authors.initials: H
authors.lastname: Tornqvist
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D052436:Adipose Tissue, White / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004950:Esterases / Q000502:physiology; D008049:Lipase; D008066:Lipolysis; D051379:Mice; D018345:Mice, Knockout; D002787:Sterol Esterase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D002265:Carboxylic Ester Hydrolases; D004950:Esterases; D008049:Lipase; D002787:Sterol Esterase; D014280:Triglycerides; C492986:Abhd5 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases