Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members
Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members
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DOI：
10.1194/jlr.m500290-jlr200
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发表时间：
2005-11-01
影响因子：
6.5
通讯作者：
Gimeno, RE
中科院分区：
文献类型：
--
作者：
Lake, AC;Sun, Y;Gimeno, RE
Adiponutrin 和相关蛋白脂肪细胞甘油三酯脂肪酶（ATGL；也称为 Desnutrin）最近被描述为具有脂质水解酶活性的脂肪细胞特异性蛋白。利用生物信息学，我们确定了另外三个 Adiponutrin 家族成员（GS2、GS2-Like 和 PNPLA1）。在这里，我们报告了 GS2 和 GS2-Like 与 Adiponutrin 和 Desnutrin/ATGL 相比的表达、调节和活性。 GS2-Like 的表达和调节方式与 Adiponutrin 类似；然而，mRNA 的绝对水平显着低于 Adiponutrin 或 Desnutrin/ATGL。 GS2 转录本仅在人类中被发现，并且在脂肪和其他组织中高度表达。所有四种蛋白质均在体外显示脂肪酶活性，这取决于 Adiponutrin、Desnutrin/ATGL 和 GS2 活性位点丝氨酸的存在。 Desnutrin/ATGL、GS2 和 GS2-Like 的过度表达（而非 Adiponutrin）会降低细胞内甘油三酯水平。这与 Desnutrin/ATGL、GS2 和 GS2-Like 在脂肪分解中的功能一致，但与 Adiponutrin 不同。与之前报道的数据一致，脂肪组织中的 Desnutrin/ATGL 因禁食而上调，而 Adiponutrin 则下调。此外，Adiponutrin 和 GS2-Like，而非 Desnutrin/ATGL，在 ob/ob 小鼠的肝脏中被强烈诱导。我们的数据支持 Adiponutrin 和 Desnutrin/ATGL 的不同功能，并提出了 GS2 可能对人类脂肪组织中的脂肪分解有显着贡献的可能性。
Adiponutrin and a related protein, adipocyte triglyceride lipase (ATGL; also known as Desnutrin), were recently described as adipocyte-specific proteins with lipid hydrolase activity. Using bioinformatics, we identified three additional Adiponutrin family members (GS2, GS2- Like, and PNPLA1). Here, we report on the expression, regulation, and activity of GS2 and GS2-Like compared with Adiponutrin and Desnutrin/ATGL. GS2- Like is expressed and regulated in a manner similar to Adiponutrin; however, the absolute levels of mRNA are significantly lower than those of Adiponutrin or Desnutrin/ATGL. GS2 transcripts were identified only in humans and are highly expressed in adipose as well as other tissues. All four proteins show lipase activity in vitro, which is dependent on the presence of the active site serine for Adiponutrin, Desnutrin/ATGL, and GS2. Overexpression of Desnutrin/ATGL, GS2, and GS2-Like, but not Adiponutrin, decreases intracellular triglyceride levels. This is consistent with a function for Desnutrin/ATGL, GS2, and GS2-Like in lipolysis, but not for Adiponutrin. Consistent with previously reported data, Desnutrin/ATGL is upregulated by fasting in adipose tissue, whereas Adiponutrin is downregulated. Additionally, Adiponutrin and GS2-Like, but not Desnutrin/ATGL, are strongly induced in the liver of ob/ob mice. Our data support distinct functions for Adiponutrin and Desnutrin/ATGL and raise the possibility that GS2 may contribute significantly to lipolysis in human adipose tissue.