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
Institute of Molecular Biosciences, University of Graz, Austria.
Science. 2006 May 5;312(5774):734-7. 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.
脂肪组织是脊椎动物中最重要的能量储存库。储存脂肪中游离脂肪酸（FFAs）的释放需要脂肪酶的酶活性。我们发现，小鼠体内脂肪甘油三酯脂肪酶（ATGL）的基因失活会增加脂肪量，并导致三酰甘油在多个组织中沉积。缺乏ATGL的小鼠心脏中积累了大量脂质，导致心脏功能障碍和过早死亡。冷适应缺陷表明该酶为产热提供FFAs。源自ATGL的FFAs可用性降低导致葡萄糖利用增加、葡萄糖耐量增加和胰岛素敏感性增加。这些结果表明，ATGL在细胞脂肪储存的分解代谢中起限速作用，并在能量稳态中发挥重要作用。
