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

American Association for the Advancement of Science (AAAS) - Tập 312 Số 5774 - Trang 734-737 - 2006
Guenter Haemmerle1,2,3,4,5, Achim Lass1,2,3,4,5, Robert Zimmermann1,2,3,4,5, Gregor Gorkiewicz1,2,3,5, Carola W. Meyer1,2,3,5, Jan Rozman1,2,3,5, Gerhard Heldmaier1,2,3,5, Robert Maier1,2,3,5, Christian Theussl1,2,3,4,5, Sandra Eder1,2,3,4,5, Dagmar Kratky1,2,3,5, Erwin F. Wagner1,2,3,4,5, Martin Klingenspor1,2,3,5, Gerald Höefler1,2,3,5, Rudolf Zechner1,2,3,4,5
1Department of Animal Physiology, Faculty of Biology, Philipps-University, Marburg, Germany
2Department of Cardiology, Center of Molecular Medicine, Medical University of Graz, Austria.
3Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Austria
4Institute of Molecular Biosciences, University of Graz, Austria
5Institute of Pathology, Center of Molecular Medicine, Medical University of Graz, Austria.

Tóm tắt

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.

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We thank H. Braunias A. Haumer A. Hermann B. Juritsch H. Reicher C. Schober R. Schreiber and G. Szerencsi for administrative and technical assistance; Siemens Medical Solutions for providing the echo machine and transducer; and E. Zechner for critically reviewing the manuscript. Supported by the Austrian Fonds zur Förderung der Wissenschaftlichen Forschung (SFB-Biomembranes F00701 and F00713) and the Austrian Federal Ministry of Education Science and Culture (GEN-AU project Genomics of Lipid-associated Disorders–GOLD) and the NGFN2 Neuronet Obesity and Related Disorders (FKZ01GS0483).

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American Association for the Advancement of Science (AAAS)

Tập 312 Số 5774

734-737

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