Abstract：
BACKGROUND: 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.
OBJECTIVE: To review the histopathology of hepatic steatosis and its mechanisms of development and to identify common and rare disease associations.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: To review the histopathology of hepatic steatosis and its mechanisms of development and to identify common and rare disease associations.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：肝脏脂肪变性是肝脏组织病理学的常见发现，也是代谢功能障碍相关脂肪变性肝病（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。
目的：回顾肝脏脂肪变性的组织病理学及其发展机制，并确定常见和罕见的疾病关联。
方法：我们使用PubMed数据库回顾了有关脂滴（LD）生物学的基础科学以及与肝性脂肪变性相关的急性和慢性肝病的临床研究的文献。
结果：多种遗传和环境因素导致慢性肝性脂肪变性或脂肪变性肝病的发展，通常表现为大泡状。微囊性脂肪变性与急性线粒体功能障碍和肝功能衰竭有关。调节异常导致脂肪变性发展的肝细胞中的脂肪代谢过程包括脂蛋白颗粒的分泌，从血液中摄取残留的脂蛋白颗粒或游离脂肪酸，从头脂肪生成，脂肪酸的氧化，脂解和吸脂。肝脏胰岛素抵抗是MASLD的关键特征。Seipin是促进LD生物发生的多功能蛋白。丙型肝炎病毒的组装发生在LD表面上。LD很重要，与内质网和其他细胞器的功能接触。
结论：多种肝脏病理与肝脏脂肪变性相关，MASLD是最重要的贡献者。肝细胞中LD的生物发生和动力学是复杂的，需要进一步研究。细胞层界面允许共同调节脂质代谢，以使潜在有毒的脂质种类的产生与其LD储库存储相匹配。
目的：回顾肝脏脂肪变性的组织病理学及其发展机制，并确定常见和罕见的疾病关联。
方法：我们使用PubMed数据库回顾了有关脂滴（LD）生物学的基础科学以及与肝性脂肪变性相关的急性和慢性肝病的临床研究的文献。
结果：多种遗传和环境因素导致慢性肝性脂肪变性或脂肪变性肝病的发展，通常表现为大泡状。微囊性脂肪变性与急性线粒体功能障碍和肝功能衰竭有关。调节异常导致脂肪变性发展的肝细胞中的脂肪代谢过程包括脂蛋白颗粒的分泌，从血液中摄取残留的脂蛋白颗粒或游离脂肪酸，从头脂肪生成，脂肪酸的氧化，脂解和吸脂。肝脏胰岛素抵抗是MASLD的关键特征。Seipin是促进LD生物发生的多功能蛋白。丙型肝炎病毒的组装发生在LD表面上。LD很重要，与内质网和其他细胞器的功能接触。
结论：多种肝脏病理与肝脏脂肪变性相关，MASLD是最重要的贡献者。肝细胞中LD的生物发生和动力学是复杂的，需要进一步研究。细胞层界面允许共同调节脂质代谢，以使潜在有毒的脂质种类的产生与其LD储库存储相匹配。
