Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD.
Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD.
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DOI：
10.1016/j.molmet.2020.101115
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发表时间：
2021-08
影响因子：
8.1
通讯作者：
Mashek DG
中科院分区：
文献类型：
--
作者：
Mashek DG
非酒精性脂肪性肝病（NAFLD）的定义是肝细胞中脂滴（ld）的丰度。虽然历史上认为ld只是能量储存的仓库，但人们越来越认识到ld影响广泛的生物过程，影响细胞代谢、信号传导和功能。虽然在了解LD积累（即脂肪变性）及其发展为NAFLD晚期和/或全身性代谢功能障碍的因素方面取得了进展，但仍有许多问题有待解决。本文综述了LD生物学的许多方面。我们简要概述了脂质增加和降解的主要途径，这些途径有助于脂肪变性，以及它们如何在NAFLD中发生改变。主要的焦点是ld和细胞功能之间的关系，以及NAFLD和全身合并症的严重程度和进展导致脂肪变性或不导致脂肪变性的详细机制。LD内或LD上的特定脂质和蛋白质作为决定LD积累是否与细胞和代谢功能障碍相关的关键成分的重要性被提出。我们讨论了LD生物学的新兴领域和未来的研究方向，以促进我们对LD在NAFLD病因学中的作用的理解。LD分解的损伤似乎有助于疾病进展，但脂肪酸（FAs）与含有LD的三酰甘油（TAG）的无效结合以及随之而来的FA分配的变化也影响NAFLD的病因。肝细胞LD丰度升高并不一定等同于细胞功能障碍。虽然LD积累是大多数NAFLD病例的先决条件，但LD的蛋白质和脂质组成是决定单纯脂肪变性进展的关键因素。进一步明确将ld与代谢功能障碍联系起来的详细分子机制对于设计针对NAFLD及其合并症的有效治疗方法至关重要。许多途径有助于肝ld的合成和降解。ld的蛋白质和脂质组成在很大程度上决定了脂肪变性是否与局部或全身代谢功能障碍耦合或不耦合。遗传变异提供了将ld与NAFLD病因联系起来的机制的见解。尽管已知LD在NAFLD中积累具有异质性，但对LD代谢的空间调节知之甚少。
Non-alcoholic fatty liver disease (NAFLD) is defined by the abundance of lipid droplets (LDs) in hepatocytes. While historically considered simply depots for energy storage, LDs are increasingly recognized to impact a wide range of biological processes that influence cellular metabolism, signaling, and function. While progress has been made toward understanding the factors leading to LD accumulation (i.e. steatosis) and its progression to advanced stages of NAFLD and/or systemic metabolic dysfunction, much remains to be resolved. This review covers many facets of LD biology. We provide a brief overview of the major pathways of lipid accretion and degradation that contribute to steatosis and how they are altered in NAFLD. The major focus is on the relationship between LDs and cell function and the detailed mechanisms that couple or uncouple steatosis from the severity and progression of NAFLD and systemic comorbidities. The importance of specific lipids and proteins within or on LDs as key components that determine whether LD accumulation is linked to cellular and metabolic dysfunction is presented. We discuss emerging areas of LD biology and future research directions that are needed to advance our understanding of the role of LDs in NAFLD etiology. Impairments in LD breakdown appear to contribute to disease progression, but inefficient incorporation of fatty acids (FAs) into LD-containing triacylglycerol (TAG) and the consequential changes in FA partitioning also affect NAFLD etiology. Increased LD abundance in hepatocytes does not necessarily equate to cellular dysfunction. While LD accumulation is the prerequisite step for most NAFLD cases, the protein and lipid composition of LDs are critical factors in determining the progression from simple steatosis. Further defining the detailed molecular mechanisms linking LDs to metabolic dysfunction is important for designing effective therapeutic approaches targeting NAFLD and its comorbidities. Numerous pathways contribute to the synthesis and degradation of hepatic LDs. The protein and lipid composition of LDs largely dictate whether steatosis is coupled or uncoupled from local or systemic metabolic dysfunction. Genetic variants provide insights into mechanisms that link LDs to NAFLD etiology. The spatial regulation of LD metabolism is poorly understood despite known heterogeneity in LD accumulation with NAFLD.
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DOI：
10.1002/hep.29273
发表时间：
2017-10
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
BasuRay S;Smagris E;Cohen JC;Hobbs HH
通讯作者：
Hobbs HH
影响因子：
13.5
作者：
Bril, Fernando;Barb, Diana;Cusi, Kenneth
通讯作者：
Cusi, Kenneth
植物化学虎杖甙通过恢复溶酶体功能和自噬通量来改善非酒精性脂肪性肝炎
影响因子：
5.3
作者：
Chen, Xiaoting;Chan, Hung;Wu, William K. K.
通讯作者：
Wu, William K. K.
影响因子：
6.5
作者：
Bu, So Young;Mashek, Douglas G.
通讯作者：
Mashek, Douglas G.
影响因子：
8.2
作者：
Amrutkar, Manoj;Kern, Matthias;Mahlapuu, Margit
通讯作者：
Mahlapuu, Margit