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Science 5 May 2006:
Vol. 312. no. 5774, pp. 734 - 737
DOI: 10.1126/science.1123965
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Reports

Defective Lipolysis and Altered Energy Metabolism in Mice Lacking Adipose Triglyceride Lipase

Guenter Haemmerle,1 Achim Lass,1 Robert Zimmermann,1 Gregor Gorkiewicz,2 Carola Meyer,5 Jan Rozman,5 Gerhard Heldmaier,5 Robert Maier,3 Christian Theussl,6 Sandra Eder,1 Dagmar Kratky,4 Erwin F. Wagner,6 Martin Klingenspor,5 Gerald Hoefler,2 Rudolf Zechner1*

Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.

1 Institute of Molecular Biosciences, University of Graz, Austria.
2 Institute of Pathology, Center of Molecular Medicine, Medical University of Graz, Austria.
3 Department of Cardiology, Center of Molecular Medicine, Medical University of Graz, Austria.
4 Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Austria.
5 Department of Animal Physiology, Faculty of Biology, Philipps-University Marburg, Germany.
6 Research Institute of Molecular Pathology, Vienna, Austria.

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

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