出版社：American Society for Biochemistry and Molecular Biology
摘要：Although lipid-rich microdomains of hepatocyte plasma membranes serve as the major scaffolding regions for cholesterol transport proteins important in cholesterol disposition, little is known regarding intracellular factors regulating cholesterol distribution therein. On the basis of its ability to bind cholesterol and alter hepatic cholesterol accumulation, the cytosolic liver type FA binding protein (L-FABP) was hypothesized to be a candidate protein regulating these microdomains. Compared with wild-type hepatocyte plasma membranes, L-FABP gene ablation significantly increased the proportion of cholesterol-rich microdomains. Lack of L-FABP selectively increased cholesterol, phospholipid (especially phosphatidylcholine), and branched-chain FA accumulation in the cholesterol-rich microdomains. These cholesterol-rich microdomains are important, owing to enrichment therein of significant amounts of key transport proteins involved in uptake of cholesterol [SR-B1, ABCA-1, P-glycoprotein (P-gp), sterol carrier binding protein (SCP-2)], FA transport protein (FATP), and glucose transporters 1 and 2 (GLUT1, GLUT2) insulin receptor. L-FABP gene ablation enhanced the concentration of SCP-2, SR-B1, FATP4, and GLUT1 in the cholesterol-poor microdomains, with functional implications in HDL-mediated uptake and efflux of cholesterol. Thus L-FABP gene ablation significantly impacted the proportion of cholesterol-rich versus -poor microdomains in the hepatocyte plasma membrane and altered the distribution of lipids and proteins involved in cholesterol uptake therein.
关键词：fatty acid ; cholesterol ; high density lipoprotein ; lipids ; liver ; membranes ; hepatocytes
