Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase
Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase
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DOI：
10.1126/science.1123965
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发表时间：
2006-05-05
期刊：
影响因子：
56.9
通讯作者：
Zechner, R
中科院分区：
文献类型：
--
作者：
Haemmerle, G;Lass, A;Zechner, R
脂肪组织是脊椎动物最重要的能量储存库。从储存的脂肪中释放游离脂肪酸（FFA）需要脂肪酶的酶活性。我们发现，小鼠脂肪甘油三酯脂肪酶（ATGL）的基因失活增加了脂肪量，并导致三酰甘油在多种组织中的沉积。ATGL缺陷小鼠在心脏中积累大量脂质，导致心脏功能障碍和过早死亡。有缺陷的冷适应表明，该酶提供FFA燃料产热。ATGL衍生的FFA的可用性降低导致葡萄糖使用增加、葡萄糖耐量增加和胰岛素敏感性增加。这些结果表明，ATGL在细胞脂肪库的催化中是限速的，并且在能量稳态中起重要作用。
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.