Center for Translational Biomedical Research, North Carolina Research Campus, University of North Carolina at Greensboro, Kannapolis, NC 28081, USA.
Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27412, USA.
Biomolecules. 2021 Dec 31;12(1):57. doi: 10.3390/biom12010057.
The liver is extremely active in oxidizing triglycerides (TG) for energy production. An imbalance between TG synthesis and hydrolysis leads to metabolic disorders in the liver, including excessive lipid accumulation, oxidative stress, and ultimately liver damage. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme that catalyzes the first step of TG breakdown to glycerol and fatty acids. Although its role in controlling lipid homeostasis has been relatively well-studied in the adipose tissue, heart, and skeletal muscle, it remains largely unknown how and to what extent ATGL is regulated in the liver, responds to stimuli and regulators, and mediates disease progression. Therefore, in this review, we describe the current understanding of the structure-function relationship of ATGL, the molecular mechanisms of ATGL regulation at translational and post-translational levels, and-most importantly-its role in lipid and glucose homeostasis in health and disease with a focus on the liver. Advances in understanding the molecular mechanisms underlying hepatic lipid accumulation are crucial to the development of targeted therapies for treating hepatic metabolic disorders.
肝脏在氧化甘油三酯（TG）以产生能量方面非常活跃。TG 的合成和水解之间的失衡会导致肝脏的代谢紊乱，包括脂质过度积累、氧化应激，最终导致肝损伤。脂肪甘油三酯脂肪酶（ATGL）是催化 TG 分解为甘油和脂肪酸的限速酶。尽管其在脂肪组织、心脏和骨骼肌中控制脂质动态平衡的作用已经得到了较为充分的研究，但 ATGL 在肝脏中的调节方式、对刺激和调节剂的反应以及在疾病进展中的介导作用仍知之甚少。因此，在这篇综述中，我们描述了 ATGL 的结构-功能关系的最新认识，包括其在翻译和翻译后水平的调节的分子机制，以及——最重要的是——其在健康和疾病状态下肝脏内脂质和葡萄糖动态平衡中的作用，重点是肝脏。深入了解肝脏脂质积累的分子机制对于开发治疗肝脏代谢紊乱的靶向疗法至关重要。
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