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

• Published in: Biochimica et biophysica acta Vol. 1863; no. 7; pp. 726 - 733
• Main Authors: Wang, Yifeng, Ding, Wen-Xing, Li, Tiangang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2018
• Subjects: Animals; atherosclerosis; Atherosclerosis - metabolism; Atherosclerosis - pathology; Autophagy; bile; bile acids; Bile Acids and Salts - metabolism; cholesterol; Cholesterol - metabolism; energy; Enterohepatic circulation; fatty liver; Fatty Liver - metabolism; Fatty Liver - pathology; Hepatocyte; hepatocytes; Hepatocytes - metabolism; Hepatocytes - pathology; homeostasis; Humans; Hyperlipidemia; inflammation; Lipid Metabolism; liver; Liver - cytology; Liver - metabolism; Liver - pathology; Liver injury; Macrophage; macrophages; Macrophages - metabolism; Macrophages - pathology; Nuclear receptor; Nutrient signaling; pathogenesis; Hepatocyte; VLDL; mTOR; oxLDL; ASMase; ASBT; SHP; LC3; ApoB100; ABCG5; BSEP; n-3 PUFA; Hyperlipidemia; TFEB; CESD; ER; Liver injury; Enterohepatic circulation; AMPK; FC; ABCG1; Macrophage; NPC; FXR; NAFLD; RCT; Nuclear receptor; SREBP-2; LXR; HMGCR; ACAT; Nutrient signaling; CYP7A1; HDL; Insig; LDL; NPC1L1; SCAP; S1PR2; LDLR; ABCA1; CE; NASH; FGF15; TG; ApoA-I; FGF19; LAL; FGFR4
• ISSN: 1388-1981; 0006-3002; 1879-2618; 1878-2434
• DOI: 10.1016/j.bbalip.2018.04.005

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. •Disrupted cholesterol homeostasis is critically implicated in the pathogenesis of fatty liver disease and atherosclerosis.•Autophagy regulates organelle homeostasis and cellular integrity.•New studies show that cholesterol and bile acids modulate hepatic autophagy.•Autophagy regulates macrophage cholesterol homeostasis in atherosclerosis.