Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis

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.