Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol - A potential role in adipocyte lipolysis
Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol - A potential role in adipocyte lipolysis
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DOI：
10.2337/db05-0585
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发表时间：
2006-07-01
期刊：
影响因子：
7.7
通讯作者：
Ishibashi, Shun
中科院分区：
文献类型：
--
作者：
Okazaki, Hiroaki;Igarashi, Masaki;Ishibashi, Shun
脂肪分解的分子机制，如脂肪酸从脂肪组织中的动员所定义的，还没有完全理解。对具有α/β水解酶折叠、丝氨酸酯酶的GXSXG基序和His-Gly二肽基序的酶的数据库搜索提供了在3 T3-L1脂肪细胞分化期间诱导的先前未注释的基因。由于其结构与三酰甘油水解酶（TGH）有70.4%的相似性，我们暂时将该酶命名为TGH-2，将原始TGH命名为TGH-1。TGH-2在组织分布、亚细胞定位、底物特异性和调节方面也与TGH-1相似。这两种酶主要在肝脏、脂肪组织和肾脏中表达。在脂肪细胞中，它们定位于微粒体和脂肪饼中。这两种酶水解对硝基苯丁酸酯，三油酸甘油酯，和单油酸甘油酯，但不二油酸甘油酯，胆固醇油酸酯，或磷脂;短链脂肪酸酯的水解是30，000倍更有效的比长链脂肪酸三酰甘油。禁食增加了这两个基因在白色脂肪组织中的表达，而再喂食抑制了它们的表达。TGH-2的RNA沉默使3 T3-L1脂肪细胞中异丙肾上腺素刺激的甘油释放减少10%，而其过表达使甘油释放增加20%。因此，TGH-2可能在能量需求增加期间对脂肪细胞脂解作出贡献。
Molecular mechanisms underlying lipolysis, as defined by mobilization of fatty acids from adipose tissue, are not fully understood. A database search for enzymes with alpha/beta hydrolase folds, the GXSXG motif for serine esterase and the His-Gly dipeptide motif, has provided a previously unannotated gene that is induced during 3T3-L1 adipocytic differentiation. Because of its remarkable structural resemblance to triacylglycerol hydrolase (TGH) with 70.4% identity, we have tentatively designated this enzyme as TGH-2 and the original TGH as TGH-1. TGH-2 is also similar to TGH-1 in terms of tissue distribution, subcellular localization, substrate specificity, and regulation. Both enzymes are predominantly expressed in liver, adipose tissue, and kidney. In adipocytes, they are localized in microsome and fatcake. Both enzymes hydrolyzed p-nitophenyl butyrate, triolein, and monoolein but not diolein, cholesteryl oleate, or phospholipids; hydrolysis of short-chain fatty acid ester was 30,000-fold more efficient than that of long-chain fatty acid triacylglycerol. Fasting increased the expression of both genes in white adipose tissue, whereas refeeding suppressed their expression. RNA silencing of TGH-2 reduced isoproterenol-stimulated glycerol release by 10% in 3T3-L1 adipocytes, while its overexpression increased the glycerol release by 20%. Thus, TGH-2 may make a contribution to adipocyte lipoly-sis during period of increased energy demand.