Kralisch Susan, Klein Johannes, Lossner Ulrike, Bluher Matthias, Paschke Ralf, Stumvoll Michael, Fasshauer Mathias
University of Leipzig, Department of Internal Medicine III, Leipzig, Germany.
Mol Cell Endocrinol. 2005 Aug 30;240(1-2):43-9. doi: 10.1016/j.mce.2005.06.002.
Recently, adipose triglyceride lipase (ATGL, also called desnutrin and calcium-independent phospholipase A2 [iPLA(2)] zeta) was isolated as a novel adipose-expressed triglyceride lipase which is downregulated in obesity and may contribute to obesity-associated metabolic disorders such as hyperlipidemia and insulin resistance. To clarify expression and regulation of this fat-derived lipase, ATGL mRNA was measured in 3T3-L1 adipocytes by quantitative real-time reverse transcription-polymerase chain reaction after treatment with isoproterenol, tumor necrosis factor (TNF) alpha, insulin, and growth hormone (GH) which have been shown to influence lipolysis and insulin sensitivity profoundly. Interestingly, treatment of adipocytes with 100 nM isoproterenol, 30 ng/ml TNF alpha, and 100 nM insulin for 16 h significantly decreased ATGL mRNA to 74%, 17%, and 49% of control levels, respectively. GH did not influence ATGL synthesis. The effect of isoproterenol, TNFalpha, and insulin on ATGL expression was time- and dose-dependent. Similarly, HSL mRNA was downregulated by the three hormones. Furthermore, signaling studies suggested that activation of Gs-protein-coupled pathways by forskolin and cholera toxin is sufficient to significantly downregulate ATGL mRNA. Moreover, p44/42 mitogen-activated protein kinase appears to partly mediate the negative effect of insulin but not TNFalpha on ATGL. Taken together, downregulation of ATGL by isoproterenol, TNFalpha, and insulin might contribute to dysregulated expression and function of this lipase in obesity, hyperlipidemia, and insulin resistance.
最近，脂肪甘油三酯脂肪酶（ATGL，也称为去营养蛋白和钙非依赖性磷脂酶A2 [iPLA(2)] ζ）被分离出来，它是一种新的脂肪组织表达的甘油三酯脂肪酶，在肥胖症中表达下调，可能与肥胖相关的代谢紊乱如高脂血症和胰岛素抵抗有关。为了阐明这种脂肪源性脂肪酶的表达和调控，在用异丙肾上腺素、肿瘤坏死因子（TNF）α、胰岛素和生长激素（GH）处理后，通过定量实时逆转录-聚合酶链反应在3T3-L1脂肪细胞中测量ATGL mRNA，这些物质已被证明对脂肪分解和胰岛素敏感性有深远影响。有趣的是，用100 nM异丙肾上腺素、30 ng/ml TNFα和100 nM胰岛素处理脂肪细胞16小时后，ATGL mRNA分别显著降低至对照水平的74%、17%和49%。GH不影响ATGL的合成。异丙肾上腺素、TNFα和胰岛素对ATGL表达的影响具有时间和剂量依赖性。同样，这三种激素也下调了激素敏感脂肪酶（HSL）mRNA的表达。此外，信号转导研究表明，福司柯林和霍乱毒素激活Gs蛋白偶联途径足以显著下调ATGL mRNA。此外，p44/42丝裂原活化蛋白激酶似乎部分介导了胰岛素对ATGL的负面影响，但不介导TNFα对ATGL的负面影响。综上所述，异丙肾上腺素、TNFα和胰岛素对ATGL的下调可能导致这种脂肪酶在肥胖、高脂血症和胰岛素抵抗中表达和功能失调。
