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

• Published in: Science (American Association for the Advancement of Science) 2006-05, Vol.312 (5774), p.734-737
• Main Authors: Haemmerle, Guenter, Lass, Achim, Zimmermann, Robert, Gorkiewicz, Gregor, Meyer, Carola, Rozman, Jan, Heldmaier, Gerhard, Maier, Robert, Theussl, Christian, Eder, Sandra, Kratky, Dagmar, Wagner, Erwin F, Klingenspor, Martin, Hoefler, Gerald, Zechner, Rudolf
• Format: Article
• Language: English
• Subjects: Adipocytes - cytology; Adipocytes - metabolism; adipose tissue; Adipose Tissue - anatomy & histology; Adipose Tissue - enzymology; Adipose Tissue - metabolism; Adipose Tissue, Brown - enzymology; Adipose tissues; adipose triglyceride lipase; Animals; Atgl gene; Biological and medical sciences; Blood Glucose - metabolism; Body fat; Carboxylic Ester Hydrolases - deficiency; Carboxylic Ester Hydrolases - genetics; Carboxylic Ester Hydrolases - metabolism; Cell Size; cold tolerance; Energy Metabolism; enzyme deficiencies; Enzymes; Fasting; Fatty Acids, Nonesterified - blood; Fatty Acids, Nonesterified - metabolism; Female; Fundamental and applied biological sciences. Psychology; Glucose; Heart; heart diseases; Heart Failure - pathology; histochemistry; Homeostasis; Insulin; Insulin - blood; Isoproterenol - pharmacology; Kidney - metabolism; knockout mutants; Lipase - deficiency; Lipase - genetics; Lipase - metabolism; Lipids; Lipids - blood; Lipolysis; Lipolysis - drug effects; Liver; Male; Metabolism; Mice; mortality; mutagenesis; Myocardium; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Nonesterified fatty acids; Oxygen Consumption; phenotype; Rodents; Testis - metabolism; Thermogenesis; triacylglycerol lipase; Triglycerides; Triglycerides - metabolism; Ventricular Dysfunction, Left - physiopathology; Vertebrates: skin, associated glands, phaneres, light organs, various exocrine glands (salt gland, uropygial gland...), adipose tissue, connective tissue
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1123965

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.