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Science 19 November 2004:
Vol. 306. no. 5700, pp. 1383 - 1386
DOI: 10.1126/science.1100747
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Reports

Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase

Robert Zimmermann,1* Juliane G. Strauss,1* Guenter Haemmerle,1 Gabriele Schoiswohl,1 Ruth Birner-Gruenberger,3 Monika Riederer,1 Achim Lass,1 Georg Neuberger,2 Frank Eisenhaber,2 Albin Hermetter,3 Rudolf Zechner1{dagger}

Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.

1 Institute of Molecular Biosciences, University of Graz, Graz, Austria.
2 Research Institute of Molecular Pathology, Vienna, Austria.
3 Institute of Biochemistry, Graz University of Technology, Austria.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: rudolf.zechner{at}uni-graz.at

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Control of Adipose Triglyceride Lipase Action by Serine 517 of Perilipin A Globally Regulates Protein Kinase A-stimulated Lipolysis in Adipocytes.
H. Miyoshi, J. W. Perfield II, S. C. Souza, W.-J. Shen, H.-H. Zhang, Z. S. Stancheva, F. B. Kraemer, M. S. Obin, and A. S. Greenberg (2007)
J. Biol. Chem. 282, 996-1002
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Roles and origins of leukocyte lipid bodies: proteomic and ultrastructural studies.
H.-C. Wan, R. C. N. Melo, Z. Jin, A. M. Dvorak, and P. F. Weller (2007)
FASEB J 21, 167-178
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Adipose Triglyceride Lipase and Hormone-sensitive Lipase Are the Major Enzymes in Adipose Tissue Triacylglycerol Catabolism.
M. Schweiger, R. Schreiber, G. Haemmerle, A. Lass, C. Fledelius, P. Jacobsen, H. Tornqvist, R. Zechner, and R. Zimmermann (2006)
J. Biol. Chem. 281, 40236-40241
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Identification of a Lipase-linked Cell Membrane Receptor for Pigment Epithelium-derived Factor.
L. Notari, V. Baladron, J. D. Aroca-Aguilar, N. Balko, R. Heredia, C. Meyer, P. M. Notario, S. Saravanamuthu, M.-L. Nueda, F. Sanchez-Sanchez, et al. (2006)
J. Biol. Chem. 281, 38022-38037
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The main triglyceride-lipase from the insect fat body is an active phospholipase A1: identification and characterization.
E. L. Arrese, R. T. Patel, and J. L. Soulages (2006)
J. Lipid Res. 47, 2656-2667
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Insulin Action in Adipose Tissue and Muscle in Hypothyroidism.
G. Dimitriadis, P. Mitrou, V. Lambadiari, E. Boutati, E. Maratou, D. B. Panagiotakos, E. Koukkou, M. Tzanela, N. Thalassinos, and S. A. Raptis (2006)
J. Clin. Endocrinol. Metab. 91, 4930-4937
   Abstract »    Full Text »    PDF »
{beta}-Cell Lipases and Insulin Secretion.
M. Fex, S. Lucas, M. S. Winzell, B. Ahren, C. Holm, and H. Mulder (2006)
Diabetes 55, S24-S31
   Abstract »    Full Text »    PDF »
Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine.
C. Prats, M. Donsmark, K. Qvortrup, C. Londos, C. Sztalryd, C. Holm, H. Galbo, and T. Ploug (2006)
J. Lipid Res. 47, 2392-2399
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Role of adipose differentiation-related protein in lung surfactant production: a reassessment.
A. L. Magra, P. S. Mertz, J. S. Torday, and C. Londos (2006)
J. Lipid Res. 47, 2367-2373
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Type II nuclear hormone receptors, coactivator, and target gene repression in adipose tissue in the acute-phase response.
B. Lu, A. H. Moser, J. K. Shigenaga, K. R. Feingold, and C. Grunfeld (2006)
J. Lipid Res. 47, 2179-2190
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Adrenergic regulation of HSL serine phosphorylation and activity in human skeletal muscle during the onset of exercise.
J. L. Talanian, R. J. Tunstall, M. J. Watt, M. Duong, C. G. R. Perry, G. R. Steinberg, B. E. Kemp, G. J. F. Heigenhauser, and L. L. Spriet (2006)
Am J Physiol Regulatory Integrative Comp Physiol 291, R1094-R1099
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Adiponutrin gene is regulated by insulin and glucose in human adipose tissue.
M. Moldes, G. Beauregard, M. Faraj, N. Peretti, P.-H. Ducluzeau, M. Laville, R. Rabasa-Lhoret, H. Vidal, and K. Clement (2006)
Eur. J. Endocrinol. 155, 461-468
   Abstract »    Full Text »    PDF »
Flavonoids Attenuate Cardiovascular Disease, Inhibit Phosphodiesterase, and Modulate Lipid Homeostasis in Adipose Tissue and Liver.
M. R. Peluso (2006)
Experimental Biology and Medicine 231, 1287-1299
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Characterization of the human patatin-like phospholipase family.
P. A. Wilson, S. D. Gardner, N. M. Lambie, S. A. Commans, and D. J. Crowther (2006)
J. Lipid Res. 47, 1940-1949
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Optimized conditions for measuring lipolysis in murine primary adipocytes.
S. Viswanadha and C. Londos (2006)
J. Lipid Res. 47, 1859-1864
   Abstract »    Full Text »    PDF »
Free Fatty acids and atherosclerosis--guilty or innocent?.
S. R. Smith and P. W. F. Wilson (2006)
J. Clin. Endocrinol. Metab. 91, 2506-2508
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Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis..
H. Okazaki, M. Igarashi, M. Nishi, M. Tajima, M. Sekiya, S. Okazaki, N. Yahagi, K. Ohashi, K. Tsukamoto, M. Amemiya-Kudo, et al. (2006)
Diabetes 55, 2091-2097
   Abstract »    Full Text »    PDF »
Functions of AMP-activated protein kinase in adipose tissue.
M. Daval, F. Foufelle, and P. Ferre (2006)
J. Physiol. 574, 55-62
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The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-{alpha} in 3T3-L1 adipocytes and is a target for transactivation by PPAR{gamma}.
J. Y. Kim, K. Tillison, J.-H. Lee, D. A. Rearick, and C. M. Smas (2006)
Am J Physiol Endocrinol Metab 291, E115-E127
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Cigarette Smoke Exposure Reprograms the Hypothalamic Neuropeptide Y Axis to Promote Weight Loss.
H. Chen, M. J. Hansen, J. E. Jones, R. Vlahos, S. Bozinovski, G. P. Anderson, and M. J. Morris (2006)
Am. J. Respir. Crit. Care Med. 173, 1248-1254
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Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase..
G. Haemmerle, A. Lass, R. Zimmermann, G. Gorkiewicz, C. Meyer, J. Rozman, G. Heldmaier, R. Maier, C. Theussl, S. Eder, et al. (2006)
Science 312, 734-737
   Abstract »    Full Text »    PDF »


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