Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Zografou, 157 84 Athens, Greece.
Gene. 2011 May 15;477(1-2):1-11. doi: 10.1016/j.gene.2011.01.007. Epub 2011 Jan 15.
The ability to store energy in the form of energy-dense triacylglycerol and to mobilize these stores rapidly during periods of low carbohydrate availability or throughout the strong metabolic demand is a highly conserved process, absolutely essential for survival. In the industrialized world the regulation of this pathway is viewed as an important therapeutic target for disease prevention. Adipose tissue lipolysis is a catabolic process leading to the breakdown of triacylglycerols stored in fat cells, and release of fatty acids and glycerol. Mobilization of adipose tissue fat is mediated by the MGL, HSL and ATGL, similarly functioning enzymes. ATGL initiates lipolysis followed by the actions of HSL on diacylglycerol, and MGL on monoacylglycerol. HSL is regulated by reversible phosphorylation on five critical residues. Phosphorylation alone, however, is not enough to activate HSL. Probably, conformational alterations and a translocation from the cytoplasm to lipid droplets are also involved. In accordance, Perilipin functions as a master regulator of lipolysis, protecting or exposing the triacylglycerol core of a lipid droplet to lipases. The prototype processes of hormonal lipolytic control are the β-adrenergic stimulation and suppression by insulin, both of which affect cytoplasmic cyclic AMP levels. Lipolysis in adipocytes is an important process in the management of body energy reserves. Its deregulation may contribute to the symptoms of type 2 diabetes mellitus and other pathological situations. We, herein, discuss the metabolic regulation and function of lipases mediating mammalian lipolysis with a focus on HSL, quoting newly identified members of the lipolytic proteome.
以高能三酰基甘油的形式储存能量，并在碳水化合物供应不足或代谢需求旺盛时迅速动员这些储存物质的能力是一种高度保守的过程，对生存绝对必要。在工业化世界中，这种途径的调节被视为预防疾病的重要治疗靶点。脂肪组织的脂解作用是一种分解代谢过程，导致脂肪细胞中储存的三酰基甘油分解，并释放脂肪酸和甘油。脂肪组织脂肪的动员是由 MGL、HSL 和 ATGL 介导的，它们是同样作用的酶。ATGL 启动脂解，随后 HSL 作用于二酰基甘油，MGL 作用于单酰基甘油。HSL 通过五个关键残基的可逆磷酸化来调节。然而，单独的磷酸化不足以激活 HSL。可能还涉及构象改变和从细胞质向脂滴的易位。相应地， perilipin 作为脂解的主要调节剂，保护或暴露脂滴的三酰基甘油核心免受脂肪酶的作用。激素脂解控制的典型过程是β-肾上腺素能刺激和胰岛素抑制，这两者都影响细胞质环腺苷酸水平。脂肪细胞中的脂解作用是管理身体能量储备的重要过程。其失调可能导致 2 型糖尿病和其他病理情况的症状。我们在此讨论介导哺乳动物脂解的脂肪酶的代谢调节和功能，重点介绍 HSL，并引用脂解蛋白组中新鉴定的成员。
