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Adipose Triglyceride Lipase (ATGL) and Hormone-Sensitive Lipase (HSL) Deficiencies Affect Expression of Lipolytic Activities in Mouse Adipose Tissues

机译:甘油三酸酯脂肪酶(ATGL)和激素敏感性脂肪酶(HSL)缺乏会影响小鼠脂肪组织中脂多糖活性的表达

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摘要

Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patters of brown and white adipose tissue from ATGL (−/−) and HSL (−/−) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols.
机译:脂肪甘油三酯脂肪酶(ATGL)和激素敏感性脂肪酶(HSL)是参与甘油三酯细胞内降解的关键酶。这项研究的目的是阐明这些蛋白质之一的缺乏如何影响脂肪组织中残留的脂解蛋白质组。为此,我们使用基于差异活性的凝胶电泳比较了来自ATGL(-/-)和HSL(-/-)小鼠的棕色和白色脂肪组织的脂肪酶谱。该方法基于具有相同底物类似结构但带有不同荧光团的活性识别探针,用于在一种电泳凝胶中特异性检测两种不同组织的酶图谱。我们发现,棕色脂肪组织中的ATGL缺乏症对该组织中其他脂解酶和酯解酶的表达水平具有深远的影响,而HSL缺乏症在棕色脂肪组织中几乎没有表现出任何作用。 ATGL缺乏或HSL缺乏都不会极大地影响白色脂肪组织中的脂肪酶模式。还对小鼠组织在酰基甘油底物上的酶活性进行了分析,显示ATGL和HSL缺陷可以至少部分被其他酶补偿。棕色脂肪组织中对ATGL缺乏反应的蛋白质被过表达,并分析了它们对酰基甘油的活性。在这些酶中,Es1,Es10和Es31-like代表脂肪酶候选物,因为它们催化长链酰基甘油的水解。

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