Background

Non-alcoholic fatty liver disease (NAFLD) is defined by the abundance of lipid droplets (LDs) in hepatocytes. While historically considered simply a depot 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 towards our understanding of 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.

Scope of review

This review will cover many facets of LD biology. We will 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 will be on the relationship between LDs and cell function and the detailed mechanisms that couple or uncouple steatosis from 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 will be presented. Finally, we will discuss emerging areas of LD biology and future research directions that are needed to advance our understanding into the role of LDs in NAFLD etiology.

Major conclusions

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 commitment 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 will be important for the design of effective therapeutic approaches targeting NAFLD and its comorbidities.

中文翻译：

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肝脏脂滴：NAFLD 中能量储存和代谢功能障碍之间的平衡作用

背景

非酒精性脂肪性肝病 (NAFLD) 由肝细胞中大量的脂滴 (LD) 定义。虽然历史上被认为只是一个能量储存库，但人们越来越认识到 LD 会影响影响细胞代谢、信号传导和功能的广泛生物过程。虽然我们在了解导致 LD 积累（即脂肪变性）的因素及其进展到 NAFLD 和/或全身代谢功能障碍的晚期阶段方面取得了进展，但仍有许多问题有待解决。

审查范围

这篇综述将涵盖 LD 生物学的许多方面。我们将简要概述导致脂肪变性的脂质积累和降解的主要途径，以及它们在 NAFLD 中是如何改变的。主要关注点将是 LD 与细胞功能之间的关系，以及将脂肪变性与 NAFLD 的严重程度和进展以及系统性合并症耦合或分离的详细机制。将介绍 LD 内或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有关的关键成分的重要性。最后，我们将讨论 LD 生物学的新兴领域和未来研究方向，以促进我们对 LD 在 NAFLD 病因学中的作用的理解。

主要结论

LD 分解的损害似乎有助于疾病进展，但脂肪酸 (FAs) 低效掺入含有 LD 的三酰基甘油 (TAG) 以及 FA 分配的相应变化也影响 NAFLD 病因。肝细胞中 LD 丰度的增加不一定等同于细胞功能障碍。虽然 LD 积累是大多数 NAFLD 病例的承诺步骤，但 LD 的蛋白质和脂质组成是确定从简单脂肪变性进展的关键因素。进一步确定将 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非常重要。