Non-alcoholic fatty liver disease (NAFLD) is a quickly emerging global health problem representing the most common chronic liver disease in the world. Atherosclerotic cardiovascular disease represents the leading cause of mortality in NAFLD patients. Cholesterol metabolism has a crucial role in the pathogenesis of both NAFLD and atherosclerosis. The liver is the major organ for cholesterol metabolism. Abnormal hepatic cholesterol metabolism not only leads to NAFLD but also drives the development of atherosclerotic dyslipidemia. The cholesterol level in hepatocytes reflects the dynamic balance between endogenous synthesis, uptake, esterification, and export, a process in which cholesterol is converted to neutral cholesteryl esters either for storage in cytosolic lipid droplets or for secretion as a major constituent of plasma lipoproteins, including very-low-density lipoproteins, chylomicrons, high-density lipoproteins, and low-density lipoproteins. In this review, we describe decades of research aimed at identifying key molecules and cellular players involved in each main aspect of hepatic cholesterol metabolism. Furthermore, we summarize the recent advances regarding the biological processes of hepatic cholesterol transport and its role in NAFLD and atherosclerosis.

非酒精性脂肪性肝病 (NAFLD) 是一个迅速出现的全球健康问题，代表了世界上最常见的慢性肝病。动脉粥样硬化性心血管疾病是 NAFLD 患者死亡的主要原因。胆固醇代谢在 NAFLD 和动脉粥样硬化的发病机制中起着至关重要的作用。肝脏是胆固醇代谢的主要器官。肝脏胆固醇代谢异常不仅会导致 NAFLD，还会导致动脉粥样硬化性血脂异常的发展。肝细胞中的胆固醇水平反映了内源性合成、摄取、酯化和输出之间的动态平衡，在这个过程中胆固醇转化为中性胆固醇酯，用于储存在细胞溶质脂滴中或作为血浆脂蛋白的主要成分分泌，包括极低密度脂蛋白、乳糜微粒、高密度脂蛋白和低密度脂蛋白。在这篇综述中，我们描述了几十年来旨在确定参与肝脏胆固醇代谢每个主要方面的关键分子和细胞参与者的研究。此外，我们总结了肝胆固醇转运的生物学过程及其在 NAFLD 和动脉粥样硬化中的作用的最新进展。