Effect of phosphatidylcholine molecular species on the uptake of HDL triglycerides and cholesteryl esters by the liver.
It has previously been shown that the hydrolysis of high density lipoprotein (HDL) phospholipids by hepatic lipase promotes the hepatic uptake of triglyceride and cholesteryl ester from HDL. Since the hydrolysis of HDL phospholipids promotes HDL cholesteryl ester uptake, then it is possible that the hepatic metabolism of HDL could be altered by changing the molecular species composition of HDL phosphatidylcholine (PC) (the major phospholipid in HDL). To test this possibility the uptake of [3H]triolein and [14C]cholesteryl oleate by the isolated perfused rat liver was determined in a nonrecirculating perfusion system following a bolus injection of reconstituted HDL (rHDL) prepared with rat serum HDL apolipoproteins, [3H]triolein, [14C]cholesteryl oleate, unesterified cholesterol, and one of five molecular species of phosphatidylcholine (16:0-18:2, 16:1-16:1, 18:0-18:2, 18:1-16:0, or 20:1-20:1), 18:1-16:0 phosphatidylcholine diether, or the total phosphatidylcholine fraction isolated from rat serum HDL. The apolipoprotein profiles and lipid compositions of all the rHDL were similar. The greatest uptake of [3H]triolein was obtained with the rHDL prepared with 16:0-18:2 phosphatidylcholine. The amount of [3H]triolein taken up by the liver when the rHDL were prepared with 16:1-16:1, 18:0-18:2, 18:1-16:0, 20:1-20:1, 18:1-16:0 phosphatidylcholine diether, or rat serum HDL phosphatidylcholine was 56.7%, 51.7, 39.9%, 27.6%, 31.8%, and 84.7%, respectively, of the amount taken up from the rHDL prepared with 16:0-18:2 phosphatidylcholine. Likewise, the greatest amount of [14C]cholesteryl oleate was taken up by the liver when the rHDL was prepared with 16:0-18:2 phosphatidylcholine and the variation in [14C]cholesteryl oleate uptake from the various rHDL displayed a pattern of dependence on the phosphatidylcholine molecular species of rHDL similar to triolein uptake. The variation in the rate of rHDL phosphatidylcholine hydrolysis by hepatic lipase in vitro as a function of the PC molecular species composition of the rHDL also resembled the variation in the hepatic uptake of [14C]cholesteryl oleate and [3H]triolein. Partial substitution of rHDL phosphatidylcholine with the minor phospholipids isolated from rat serum HDL affected neither the hepatic uptake of [3H]triolein or [14C]cholesteryl oleate nor phosphatidylcholine hydrolysis by hepatic lipase in vitro when 16:0-18:2 phosphatidylcholine or rat serum HDL phosphatidylcholine was used to prepare the rHDL. On the other hand, when rHDL was prepared with 20:1-20:1 phosphatidylcholine, the inclusion of the minor phospholipids increased [3H]triolein and [14C]cholesteryl oleate uptake and phosphatidylcholine hydrolysis approximately twofold.(ABSTRACT TRUNCATED AT 400 WORDS)
Kadowaki
H
H
Division of Lipid Metabolism, Boston VA Medical Center, MA 02130.
Patton
G M
GM
Robins
S J
SJ
D000818:Animals; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006868:Hydrolysis; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism*; D014304:Triolein / Q000378:metabolism; D014316:Tritium
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; D014280:Triglycerides; D014316:Tritium; D014304:Triolein; C014409:cholesteryl oleate