7-Ketocholesterol delivered to mice in chylomicron remnant-like particles is rapidly metabolised, excreted and does not accumulate in aorta.
Cholesterol oxidation products (oxysterols) have been implicated in atherogenesis due to their presence in atherosclerotic tissue and their potent effects in vitro. One of the major oxysterols currently of interest is 7-ketocholesterol (7K) and it has been suggested that the diet is an important source of this oxysterol. This investigation tested the hypothesis that 7K, delivered in a physiologically relevant vehicle, chylomicron remnant-like emulsion (CMR), would be metabolised and excreted by mice in a similar manner and to a similar extent as previously observed in rats when delivered in a chemically modified lipoprotein, acetylated low-density lipoprotein (acLDL). Indeed, the metabolism of 14C-7K delivered in CMR mirrored that of acLDL and was much more rapid than (3)H-cholesterol delivered simultaneously. The 7K-derived (14)C was cleared from the liver, appeared in the intestine and was excreted in the faeces. A substantial proportion of the 7K-derived (14)C in the intestine and faeces was aqueous-soluble, indicating metabolism to polar products, presumably bile acids. Moreover, while cholesterol-derived (3)H increased in the aorta, (14)C appeared transiently and there was no observable accumulation within 24 h. The data confirm our previous findings of rapid hepatic metabolism of 7K when delivered in acLDL and demonstrate that 7K delivered in a vehicle of dietary significance is similarly metabolised and excreted. Indeed, the data encourage further investigation into the contribution that dietary oxysterols may or may not make to atherogenesis.
Cell Biology Group, Heart Research Institute, 145 Missenden Road, Camperdown, 2050, Sydney, N.S.W., Australia.
M A
MA
Lyons
A J
AJ
Brown
D000818:Animals; D001011:Aorta / Q000378:metabolism; D002250:Carbon Radioisotopes; D002914:Chylomicrons; D004337:Drug Carriers; D005243:Feces / Q000737:chemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007653:Ketocholesterols / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D008077:Lipoproteins, LDL; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000097:blood; D014316:Tritium; D014556:Urine / Q000737:chemistry
D002250:Carbon Radioisotopes; D002914:Chylomicrons; D004337:Drug Carriers; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D014280:Triglycerides; C032629:acetyl-LDL; D014316:Tritium; C003001:7-ketocholesterol