Department of Pediatrics, University of Kentucky, Lexington, USA.
Cell Metab. 2010 Mar 3;11(3):194-205. doi: 10.1016/j.cmet.2010.02.003.
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.
脂肪甘油三酯脂肪酶（ATGL）是脂肪细胞中甘油三酯（TAG）水解的限速酶。ATGL 调节的确切机制仍不确定。在这里，我们证明 G(0)/G(1) 开关基因 2（G0S2）编码的蛋白是 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 细胞中过表达时，G0S2 定位于脂滴并阻止它们被 ATGL 介导的降解。此外，G0S2 通过 G0S2 的疏水性结构域和 ATGL 的类脂肪酶结构域特异性地与 ATGL 相互作用。更重要的是，与 G0S2 的相互作用抑制了 ATGL 的 TAG 水解酶活性。内源性 G0S2 的敲低加速了脂肪细胞中的基础和刺激脂肪分解，而 G0S2 的过表达则降低了脂肪细胞和脂肪组织外植体中脂肪分解的速度。因此，G0S2 可在体外和体内减弱 ATGL 的作用，并通过这种机制调节 TAG 水解。
