Translational Liver Research, Department of Medical Cell BioPhysics, Faculty of Science and Technology, Technical Medical Center, University of Twente, Enschede 7500 AE, the Netherlands.
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584 CG, the Netherlands; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119074 Singapore, Singapore.
Adv Drug Deliv Rev. 2020;159:180-197. doi: 10.1016/j.addr.2020.06.027. Epub 2020 Jun 30.
The liver is the key organ involved in lipid metabolism and transport. Excessive lipid accumulation due to dysregulated lipid metabolism predisposes the liver to steatosis, cirrhosis, and hepatocellular carcinoma. Lipids are generally compartmentalized in specialized organelles called lipid droplets that enable cells to store and release lipids in a regulated manner. However, during flux-in and flux-out of droplets, lipids are converted into toxic species leading to lipid-mediated liver damage. Lipids are categorized into 'toxic' or 'healthy' lipids that are involved in liver disease pathogenesis or resolution, respectively. Lipidomic analysis have revealed unique lipid signature that correlates with the disease progression therefore being used for disease diagnosis. In this comprehensive review, we provide an overview on hepatic lipid homeostasis, lipid compartmentalization mechanisms and lipidomic profiles in different liver diseases. We further discuss promising therapeutics targeting the hepatic lipidome including pro-resolving lipids, liposomes, and small-molecule inhibitors for the treatment of liver diseases.
肝脏是参与脂质代谢和转运的关键器官。由于脂质代谢失调导致的脂质过度积累,使肝脏容易发生脂肪变性、肝硬化和肝细胞癌。脂质通常被分隔在称为脂滴的专门细胞器中,使细胞能够以受调控的方式储存和释放脂质。然而,在脂滴的流入和流出过程中,脂质会转化为有毒物质,导致脂质介导的肝损伤。脂质分为“有毒”或“健康”脂质,它们分别参与肝脏疾病的发病机制或解决。脂质组学分析揭示了与疾病进展相关的独特脂质特征,因此可用于疾病诊断。在这篇全面的综述中,我们提供了关于肝脏脂质稳态、脂质分隔机制和不同肝脏疾病的脂质组学特征的概述。我们进一步讨论了针对肝脏脂质组的有前途的治疗方法,包括促解决脂质、脂质体和小分子抑制剂,用于治疗肝脏疾病。