Cholesterol and bile acid-mediated regulation of autophagy in fatty liver diseases and atherosclerosis

Liver is the major organ that regulates whole body cholesterol metabolism. Disrupted hepatic cholesterol homeostasis contributes to the pathogenesis of nonalcoholic steatohepatitis, dyslipidemia, atherosclerosis, and cardiovascular diseases. Hepatic bile acid synthesis is the major catabolic mechanism for cholesterol elimination from the body. Furthermore, bile acids are signaling molecules that regulate liver metabolism and inflammation. Autophagy is a highly-conserved lysosomal degradation mechanism, which plays an essential role in maintaining cellular integrity and energy homeostasis. In this review, we discuss emerging evidence linking hepatic cholesterol and bile acid metabolism to cellular autophagy activity in hepatocytes and macrophages, and how these interactions may be implicated in the pathogenesis and treatment of fatty liver disease and atherosclerosis.