Intracellular Localization and Metabolism of Chylomicron Remnants in the Livers of Low Density Lipoprotein Receptor-deficient Mice and ApoE-deficient Mice

摘要: The metabolism of chylomicron remnants in mice deficient low density lipoprotein receptor (LDLr) or apolipoprotein E (apoE) was compared with that control C57BL/6J mice. Mice were injected intravenously chylomicron-like emulsions labeled radioactive lipids. Blood samples taken at fixed time intervals from the retro-orbital sinus, and clearance rates lipoproteins assessed decline plasma radioactivities. To follow intracellular pathway liver, a fluorescent cholesteryl ester (BODIPY) injected, liver sections processed assayed by laser confocal microscopy. Catabolism remnant esters injecting cholesteryl[1- 14 C]oleate measuring expired CO2 each animal. In apoE-deficient mice, removal totally impeded, while LDLr-deficient similar to micrographs livers 20 min after injection showed evenly distributed particles hepatocytes contrast, mainly located sinusoidal spaces Three hours few particles, indicating have been catabolized, still highly fluorescent. Micrographs no any injection. Measurement fatty acid moiety oleate indicated slower essentially nil Control had 50% label 3 h We conclude under normal circumstances, are rapidly internalized LDLr catabolized hepatocytes, critical requirement for apoE. When is absent, up second apoE-dependent pathway, first space subsequent slow endocytosis catabolism. Hepatic via this increased heparin, inhibited lactoferrin, heparinase, suramin, down-regulated feeding high fat diet. Chylomicrons responsible transporting most dietary lipids intestinal tract into bloodstream. Along bulk form triacylglycerols (triglycerides) phospholipids, small proportion total mass made cholesterol esters. circulation, chylomicrons metabolized two-stage process. Initially, majority triglyceride hydrolyzed action lipase extrahepatic tissues. resulting smaller known as remnants, contain residual all ester. acquired 1 removed delivered lysosomes (1). After hydrolysis hydrolase, liberated acids enter pathways oxidative carbon dioxide formed. exhaled can be quantified (2) provide measure internalization catabolism remnants.