Effects of sphingomyelin and phosphatidylcholine acyl chains on the clearance of triacylglycerol-rich lipoproteins from plasma. Studies with lipid emulsions in rats.
Series of lipid emulsions were prepared as physical models of lymph chylomicrons. The emulsion phospholipid was systematically varied with respect to sphingomyelin, in 0-100% mixtures with egg yolk phosphatidylcholine (EYPC). In other emulsions, the phospholipid was systematically varied with respect to dipalmitoylphosphatidylcholine (DPPC) in 0-100% mixtures with 1-palmitoyl-2-oleoylphosphatidylcholine (POPC). All emulsions contained unlabeled free cholesterol, radiolabeled triolein (TO) and radiolabeled cholesteryl oleate (CO). The emulsions were injected into conscious rats to measure the clearances of emulsion TO and CO and the capture of lipid radioactivity by selected organs. The emulsions containing EYPC or POPC were metabolized similarly to lymph chylomicrons, consistent with rapid lipoprotein lipase-mediated hydrolysis of emulsion TO followed by hepatic uptake of the CO in the triglyceride-depleted emulsion remnants. Emulsions stabilized with either 1-oleoyl-2-stearoyl- or 1-stearoyl-2-oleoylphosphatidylcholine (OSPC or SOPC) were metabolized similarly. Increasing amounts of sphingomyelin in EYPC emulsions progressively slowed the removal of TO and CO labels from plasma. With 50% sphingomyelin clearance was very slow, while emulsion clearance was negligible with 100% sphingomyelin. Emulsions containing 20% of DPPC in POPC were metabolized similarly to 100% POPC, but 40% or more of DPPC progressively slowed the removal from plasma of both TO and CO. With 100% DPPC clearance was characterized by a rapid initial removal of about 30% of the injected material, followed by a second phase when removal was negligible, suggesting lack of hydrolysis of triacylglycerols by lipoprotein lipase. Changes in the apolipoproteins associated with the emulsions probably mediated the observed changes in clearance.
Redgrave
T G
TG
Department of Physiology, University of Western Australia, Nedlands.
Rakic
V
V
Mortimer
B C
BC
Mamo
J C
JC
D000818:Animals; D002788:Cholesterol Esters / Q000493:pharmacokinetics; D002914:Chylomicrons; D004655:Emulsions / Q000494:pharmacology; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013109:Sphingomyelins / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism; D014280:Triglycerides / Q000097:blood*; D014304:Triolein / Q000493:pharmacokinetics
D002788:Cholesterol Esters; D002914:Chylomicrons; D004655:Emulsions; D008074:Lipoproteins; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D014280:Triglycerides; C030087:lipoprotein triglyceride; D014304:Triolein; C014409:cholesteryl oleate; C027891:1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine; C067973:1-oleoyl-2-stearoylphosphatidylcholine; D008071:Lipoprotein Lipase