Adipose triglyceride lipase - Function, regulation by insulin, and comparison with adiponutrin
Adipose triglyceride lipase - Function, regulation by insulin, and comparison with adiponutrin
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DOI：
10.2337/diabetes.55.01.06.db05-0982
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发表时间：
2006-01-01
期刊：
影响因子：
7.7
通讯作者：
Flier, JS
中科院分区：
文献类型：
--
作者：
Kershaw, EE;Hamm, JK;Flier, JS
脂肪甘油三酯脂肪酶（ATGL）是最近发现的具有甘油三酯特异性脂肪酶活性的脂肪富集蛋白。ATGL与脂降素序列同源性最大，脂降素是一种营养调节蛋白，生物学功能尚不清楚。在这里，我们介绍了ATGL和脂降素的功能分析，并描述了胰岛素对它们的调节。逆转录病毒介导的ATGL在3T3-L1脂肪细胞中的过表达增加了基础和异丙肾上腺素刺激的甘油和非酯化脂肪酸（NEFA）的释放，而sirna介导的ATGL的下调具有相反的效果。相比之下，sirna介导的3T3-L1脂肪细胞中脂降素的下调对甘油或NEFA的释放没有影响。在小鼠中，ATGL和脂降素在脂肪组织中都受到营养调节，空腹时ATGL上调，脂降素下调。在3T3-L1脂肪细胞中，胰岛素以剂量和时间依赖的方式降低ATGL并增加脂降素的表达，表明胰岛素直接介导了这种营养调节。此外，在链脲佐菌素诱导的糖尿病小鼠中，ATGL的脂肪表达在胰岛素缺乏时升高，在胰岛素替代时降低，在脂肪特异性胰岛素受体敲除小鼠中升高，而脂降素表现出相反的模式。这些数据表明，小鼠ATGL而非脂降素有助于脂肪细胞的净脂解，并且ATGL和脂降素在体内和体外均受胰岛素的相反调节。
Adipose triglyceride lipase (ATGL) is a recently described adipose-enriched protein with triglyceride-specific lipase activity. ATGL shares the greatest sequence homology with adiponutrin, a nutritionally regulated protein of unclear biological function. Here we present a functional analysis of ATGL and adiponutrin and describe their regulation by insulin. Retroviral-mediated overexpression of ATGL in 3T3-L1 adipocytes increased basal and isoproterenol-stimulated glycerol and nonesterified fatty acid (NEFA) release, whereas siRNA-mediated knockdown of ATGL had the opposite effect. In contrast, siRNA-mediated knockdown of adiponutrin in 3T3-L1 adipocytes had no effect on glycerol or NEFA release. In mice, both ATGL and adiponutrin are nutritionally regulated in adipose tissue, with ATGL being upregulated and adiponutrin being downregulated by fasting. In 3T3-L1 adipocytes, insulin decreased ATGL and increased adiponutrin expression in a dose- and time-dependent manner, suggesting that insulin directly mediates this nutritional regulation. In addition, adipose expression of ATGL was increased by insulin deficiency and decreased by insulin replacement in streptozotocin-induced diabetic mice and was increased in fat-specific insulin receptor knockout mice, whereas adiponutrin showed the opposite pattern. These data suggest that murine ATGL but not adiponutrin contributes to net adipocyte lipolysis and that ATGL and adiponutrin are oppositely regulated by insulin both in vitro and in vivo.