Institute of Molecular Biosciences, University of Graz, Austria.
Institute of Molecular Biosciences, University of Graz, Austria.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Jun;1864(6):880-899. doi: 10.1016/j.bbalip.2018.10.008. Epub 2018 Oct 25.
Adipose triglyceride lipase (ATGL) has been discovered 14 years ago and revised our view on intracellular triglyceride (TG) mobilization - a process termed lipolysis. ATGL initiates the hydrolysis of TGs to release fatty acids (FAs) that are crucial energy substrates, precursors for the synthesis of membrane lipids, and ligands of nuclear receptors. Thus, ATGL is a key enzyme in whole-body energy homeostasis. In this review, we give an update on how ATGL is regulated on the transcriptional and post-transcriptional level and how this affects the enzymes' activity in the context of neutral lipid catabolism. In depth, we highlight and discuss the numerous physiological functions of ATGL in lipid and energy metabolism. Over more than a decade, different genetic mouse models lacking or overexpressing ATGL in a cell- or tissue-specific manner have been generated and characterized. Moreover, pharmacological studies became available due to the development of a specific murine ATGL inhibitor (Atglistatin®). The identification of patients with mutations in the human gene encoding ATGL and their disease spectrum has underpinned the importance of ATGL in humans. Together, mouse models and human data have advanced our understanding of the physiological role of ATGL in lipid and energy metabolism in adipose and non-adipose tissues, and of the pathophysiological consequences of ATGL dysfunction in mice and men.
脂肪甘油三酯脂肪酶 (ATGL) 是 14 年前被发现的，它改变了我们对细胞内甘油三酯 (TG) 动员的认识——这一过程被称为脂解。ATGL 启动 TG 的水解，释放脂肪酸 (FA)，FA 是至关重要的能量底物、膜脂质合成的前体和核受体的配体。因此，ATGL 是全身能量平衡的关键酶。在这篇综述中，我们更新了 ATGL 在转录和转录后水平的调控方式，以及这如何影响酶在中性脂质代谢中的活性。深入探讨了 ATGL 在脂质和能量代谢中的众多生理功能。十多年来，已经生成并表征了多种缺乏或特异性过表达 ATGL 的基因敲除或基因过表达小鼠模型。此外，由于特异性鼠 ATGL 抑制剂（Atglistatin®）的开发，药理学研究也成为可能。鉴定出人类编码 ATGL 的基因突变患者及其疾病谱，突显了 ATGL 在人类中的重要性。总之，小鼠模型和人类数据提高了我们对 ATGL 在脂肪和非脂肪组织中脂质和能量代谢的生理作用以及 ATGL 功能障碍在小鼠和人类中的病理生理后果的理解。
