Lord Caleb C, Brown J Mark
Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Adipocyte. 2012;1(3):123-131. doi: 10.4161/adip.20035.
Catabolism of stored triacylglycerol (TAG) from cytoplasmic lipid droplets is critical for providing energy substrates, membrane building blocks, and signaling lipids in most cells of the body. However, the lipolytic machinery dictating TAG hydrolysis varies greatly among different cell types. Within the adipocyte, TAG hydrolysis is dynamically regulated by hormones to ensure appropriate metabolic adaptation to nutritional and physiologic cues. In other cell types such as hepatocytes, myocytes, and macrophages, mobilization of stored TAG is regulated quite differently. Within the last decade, mutations in two key genes involved in TAG hydrolysis, alpha-beta hydrolase domain 5 (ABHD5/CGI-58) and adipose triglyceride lipase (ATGL/PNPLA2), were found to cause two distinct neutral lipid storage diseases (NLSD) in humans. These genetic links, along with supporting evidence in mouse models, have prompted a number of studies surrounding the biochemical function(s) of these proteins. Although both CGI-58 and ATGL have been clearly implicated in TAG hydrolysis in multiple tissues and have even been shown to physically interact with each other, recent evidence suggests that they may also have distinct roles. The purpose of this review is to summarize the most recent insights into how CGI-58 and ATGL regulate lipid metabolism and signaling.
在身体的大多数细胞中，细胞质脂滴中储存的三酰甘油（TAG）的分解代谢对于提供能量底物、膜构建块和信号脂质至关重要。然而，决定TAG水解的脂解机制在不同细胞类型中差异很大。在脂肪细胞内，TAG水解受激素动态调节，以确保对营养和生理信号做出适当的代谢适应。在其他细胞类型如肝细胞、肌细胞和巨噬细胞中，储存TAG的动员调节方式则大不相同。在过去十年中，人们发现参与TAG水解的两个关键基因，即α-β水解酶结构域5（ABHD5/CGI-58）和脂肪甘油三酯脂肪酶（ATGL/PNPLA2）发生突变，会在人类中导致两种不同的中性脂质贮积病（NLSD）。这些基因关联以及小鼠模型中的支持证据，促使人们围绕这些蛋白质的生化功能开展了大量研究。尽管CGI-58和ATGL都已明确参与多种组织中的TAG水解，甚至已被证明它们在物理上相互作用，但最近的证据表明它们可能也具有不同的作用。本综述的目的是总结关于CGI-58和ATGL如何调节脂质代谢和信号传导的最新见解。
