Zimmermann Robert, Strauss Juliane G, Haemmerle Guenter, Schoiswohl Gabriele, Birner-Gruenberger Ruth, Riederer Monika, Lass Achim, Neuberger Georg, Eisenhaber Frank, Hermetter Albin, Zechner Rudolf
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Science. 2004 Nov 19;306(5700):1383-6. doi: 10.1126/science.1100747.
Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.
从脂肪组织中的甘油三酯储存中动员脂肪酸需要脂解酶。功能失调的脂解作用会影响能量稳态,并可能导致肥胖症和胰岛素抵抗的发病机制。到目前为止,激素敏感性脂肪酶(HSL)是已知的唯一一种能水解哺乳动物脂肪组织中甘油三酯的酶。在此,我们报告第二种酶,即脂肪甘油三酯脂肪酶(ATGL),催化甘油三酯水解的第一步。有趣的是,ATGL含有植物酰基水解酶共有的“马铃薯Patatin结构域”。ATGL在小鼠和人类的脂肪组织中高度表达。它对三酰甘油表现出高底物特异性,并与脂滴相关。抑制ATGL会显著降低总脂肪酰基水解酶活性。因此,ATGL和HSL协同分解哺乳动物脂肪组织中储存的甘油三酯。