Role of HDL1 in cholesteryl ester uptake in rats.
It has been suggested that apoE may play a central role in reverse cholesterol transport in rats. By this hypothesis, cholesteryl esters (CE) accumulate in high density lipoprotein (HDL) particles, which acquire apoE at the expense of apoA-I, and the apoE targets them for rapid hepatic uptake. However, the pathway has not been directly assessed in vivo. We directly traced the metabolism of HDL1 cholesteryl esters in rats. To do this, rat HDL1 was labeled in its apoE and CE moieties, and HDL2 free of apoE was labeled in its apoA-I and CE moieties; 14C- or 3H-labeled cholesteryl-oleyl ether traced the CE moieties and the 125I- or 131I-labeled N-methyltyramine cellobiose (NMTC) ligand traced the apolipoprotein moieties. The labeled HDLs were injected, plasma decays were followed, and tissues were examined after 24 h. ApoE tracer decayed from plasma 2.4-times faster than HDL1 CE and 1.8-times faster than HDL2 CE. HDL1 CE decayed significantly more slowly than HDL2 CE (0.75-times). As expected, hepatic uptake of HDL2 CE was mostly by selective (indirect) uptake. However, hepatic uptake of HDL1 CE was at a fractional rate significantly lower than that of HDL2 CE (0.69-times), even though the uptake of apoE was much higher. The plasma decay of HDL1 apoE evidently reflects in large part the uptake of apoE after transfer to other fractions, and it over-estimates the clearance of HDL1 CE. Selective uptake plays the major role in hepatic HDL CE uptake in rats.
Department of Medicine, University of California, San Diego, La Jolla 92093.
B M
BM
Richard
R C
RC
Pittman
D000818:Animals; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014316:Tritium
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL; D014316:Tritium