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The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase.

机译:G(0)/ G(1)开关基因2通过与脂肪甘油三酸酯脂肪酶缔合来调节脂肪脂解。

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摘要

Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for triacylglycerol (TAG) hydrolysis in adipocytes. The precise mechanisms whereby ATGL is regulated remain uncertain. Here, we demonstrate that a protein encoded by G(0)/G(1) switch gene 2 (G0S2) is a selective regulator of ATGL. G0S2 is highly expressed in adipose tissue and differentiated adipocytes. When overexpressed in HeLa cells, G0S2 localizes to lipid droplets and prevents their degradation mediated by ATGL. Moreover, G0S2 specifically interacts with ATGL through the hydrophobic domain of G0S2 and the patatin-like domain of ATGL. More importantly, interaction with G0S2 inhibits ATGL TAG hydrolase activity. Knockdown of endogenous G0S2 accelerates basal and stimulated lipolysis in adipocytes, whereas overexpression of G0S2 diminishes the rate of lipolysis in both adipocytes and adipose tissue explants. Thus, G0S2 functions to attenuate ATGL action both in vitro and in vivo and by this mechanism regulates TAG hydrolysis.
机译:脂肪甘油三酯脂肪酶(ATGL)是脂肪细胞中三酰基甘油(TAG)水解的限速酶。监管ATGL的确切机制仍然不确定。在这里,我们证明了由G(0)/ G(1)开关基因2(G0S2)编码的蛋白质是ATGL的选择性调节剂。 G0S2在脂肪组织和分化的脂肪细胞中高表达。当在HeLa细胞中过度表达时,GOS2定位于脂质小滴并阻止其由ATGL介导的降解。此外,G0S2通过G0S2的疏水域和ATGL的类似patatin的域与ATGL特异性相互作用。更重要的是,与G0S2的相互作用抑制了ATGL TAG水解酶的活性。内源性G0S2的敲低加速了脂肪细胞的基础和刺激的脂解作用,而G0S2的过表达降低了脂肪细胞和脂肪组织外植体的脂解率。因此,GOS2的功能是在体外和体内减弱ATGL的作用,并通过这种机制调节TAG水解。

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