Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA.
Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia, USA.
Aliment Pharmacol Ther. 2024 Jul;60(2):167-200. doi: 10.1111/apt.18059. Epub 2024 Jun 7.
Hepatic steatosis is a common finding in liver histopathology and the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), whose global prevalence is rising.
To review the histopathology of hepatic steatosis and its mechanisms of development and to identify common and rare disease associations.
We reviewed literature on the basic science of lipid droplet (LD) biology and clinical research on acute and chronic liver diseases associated with hepatic steatosis using the PubMed database.
A variety of genetic and environmental factors contribute to the development of chronic hepatic steatosis or steatotic liver disease, which typically appears macrovesicular. Microvesicular steatosis is associated with acute mitochondrial dysfunction and liver failure. Fat metabolic processes in hepatocytes whose dysregulation leads to the development of steatosis include secretion of lipoprotein particles, uptake of remnant lipoprotein particles or free fatty acids from blood, de novo lipogenesis, oxidation of fatty acids, lipolysis and lipophagy. Hepatic insulin resistance is a key feature of MASLD. Seipin is a polyfunctional protein that facilitates LD biogenesis. Assembly of hepatitis C virus takes place on LD surfaces. LDs make important, functional contact with the endoplasmic reticulum and other organelles.
Diverse liver pathologies are associated with hepatic steatosis, with MASLD being the most important contributor. The biogenesis and dynamics of LDs in hepatocytes are complex and warrant further investigation. Organellar interfaces permit co-regulation of lipid metabolism to match generation of potentially toxic lipid species with their LD depot storage.
肝脂肪变性是肝脏组织病理学中的常见表现，也是代谢功能障碍相关脂肪性肝病（MASLD）的标志，以前称为非酒精性脂肪性肝病（NAFLD），其全球患病率正在上升。
综述肝脂肪变性的组织病理学及其发生机制，并确定常见和罕见的疾病相关性。
我们使用 PubMed 数据库回顾了关于脂滴（LD）生物学基础科学和与肝脂肪变性相关的急性和慢性肝病的临床研究文献。
多种遗传和环境因素导致慢性肝脂肪变性或脂肪性肝病的发展，其通常表现为大泡性。微泡性脂肪变性与急性线粒体功能障碍和肝衰竭有关。肝细胞内脂肪代谢过程的失调导致脂肪变性的发生，包括脂蛋白颗粒的分泌、血液中残余脂蛋白颗粒或游离脂肪酸的摄取、从头合成脂肪、脂肪酸的氧化、脂肪分解和脂肪自噬。肝胰岛素抵抗是 MASLD 的一个关键特征。Seipin 是一种多功能蛋白，可促进 LD 的生物发生。丙型肝炎病毒的组装发生在 LD 表面。LD 与内质网和其他细胞器之间存在重要的、功能性的接触。
多种肝脏病理与肝脂肪变性有关，MASLD 是最重要的贡献者。肝细胞中 LD 的生物发生和动态变化非常复杂，需要进一步研究。细胞器界面允许脂质代谢的共同调节，以匹配潜在毒性脂质物种的产生与其 LD 储存库的储存。
