Adipose Triglyceride Lipase and Hormone-sensitive Lipase Are the Major Enzymes in Adipose Tissue Triacylglycerol Catabolism*
By M. Schweiger, R. Schreiber, G. Haemmerle, A. Lass, C. Fledelius, P. Jacobsen, H. Tornqvist, R. Zechner, R. Zimmermann. Journal of Biological Chemistry, 2006
699 citations recorded by the source corpus.
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.
Subfields: Biochemistry, Physiology, Surgery
View Paper: https://www.semanticscholar.org/paper/01a8dd536a4fb2b8fa016a810b87a2f45d87fa97
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Citations in the corpus
- The metabolic syndrome. (2008, background): “Although it is well accepted that this process is mediated by hormone-sensitive lipase (HSL) (128), recent evidence points to adipose triglyceride lipase as playing an additional role; and collectively these two hormones account for 95% of triglyceride hydrolysis (129).”
- Adipose tissue and adipocytes supports tumorigenesis and metastasis (2013, background): “Once the ovarian cancer cells interact with the adipocytes they initiate HSL-mediated lipolysis in the adipocyte, releasing fatty acids which are then taken up by the ovarian cancer cells for energy production.”
- Lipolysis – A highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores (2011, methodology): “After full hormonal stimulation, HSL phosphorylation and the perilipin-1 mediated translocation of the enzyme to the LD causes a 100-fold induction of HSL activity in WAT [79].”
- PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores (2009, background): “CGI-58 is an activator of the acyl hydrolase activity of ATGL [61–63].”