Intracellular localization and metabolism of chylomicron remnants in the livers of low density lipoprotein receptor-deficient mice and ApoE-deficient mice. Evidence for slow metabolism via an alternative apoE-dependent pathway

• Published in: The Journal of biological chemistry 1995-12, Vol.270 (48), p.28767-28776
• Main Authors: Mortimer, B.C. (University of Western Australia, Nedlands, Australia.), Beveridge, D.J, Martins, I.J, Redgrave, T.G
• Format: Article
• Language: English
• Subjects: alpha-Macroglobulins - pharmacology; Animals; Apolipoproteins E - deficiency; Apolipoproteins E - metabolism; BIOCHIMIE; BIOQUIMICA; CATABOLISME; CATABOLISMO; CELLULE; CELULAS; CHIMIORECEPTEUR; CHOLESTEROL; Cholesterol, Dietary - administration & dosage; CHYLOMICRON; Chylomicrons - blood; Chylomicrons - metabolism; COLESTEROL; CONSOMMATION ALIMENTAIRE; CONSUMO DE ALIMENTOS; CORPS GRAS; Dietary Fats - administration & dosage; DIOXIDO DE CARBONO; DIOXYDE DE CARBONE; EMULSION; Emulsions; ESTER; ESTERES; FOIE; GRASAS; Heparin - pharmacology; Heymann Nephritis Antigenic Complex; HIGADO; Lactoferrin - pharmacology; LIPOLISIS; LIPOLYSE; LIPOPROTEINAS; LIPOPROTEINE; Liver - drug effects; Liver - metabolism; Male; Membrane Glycoproteins - pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; QUILOMICRONES; QUIMIORECEPTORES; RATON; Rats; Rats, Wistar; Receptors, LDL - deficiency; SOURIS; Spectrometry, Fluorescence; Suramin - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.48.28767

The metabolism of chylomicron remnants in mice deficient in low density lipoprotein receptor (LDLr) or apolipoprotein E (apoE) was compared with that of control C57BL/6J mice. Mice were injected intravenously with chylomicron-like emulsions labeled with radioactive lipids. Blood samples were taken at fixed time intervals from the retro-orbital sinus, and clearance rates of the lipoproteins were assessed from the decline in plasma radioactivities. To follow the intracellular pathway of remnants in the liver, emulsions labeled with a fluorescent cholesteryl ester (BODIPY) were injected, and liver sections were processed and assayed by laser confocal microscopy. Catabolism of remnant cholesteryl esters was assessed by injecting emulsions labeled with cholesteryl[1-14C]oleate and measuring the expired CO2 from each animal. In apoE-deficient mice, remnant removal from plasma was totally impeded, while the clearance of remnants in LDLr-deficient mice was similar to that in C57BL/6J control mice. The confocal micrographs of livers 20 min after injection of fluorescent chylomicron-like emulsions showed evenly distributed fluorescent particles in the hepatocytes from control mice. In contrast, the fluorescent particles were mainly located in sinusoidal spaces in LDLr-deficient mice. Three hours after injection the livers from control mice showed few fluorescent particles, indicating that remnants have been catabolized, while the sections from LDLr-deficient mice were still highly fluorescent. Micrographs from apoE-deficient mice showed no fluorescent particles in the liver at any time after injection. Measurement of expired radioactive CO2 after injection of emulsions labeled in the fatty acid moiety of cholesteryl oleate indicated that remnant metabolism was slower in the LDLr-deficient mice and essentially nil in the apoE-deficient mice. Control mice had expired 50% of the injected label by 3 h after injection