Effects on apoB-100 secretion and bile acid synthesis by redirecting cholesterol efflux from HepG2 cells.
This study determined the effects of apoA-I, HDL3, or hydroxy-beta-cyclodextrin on apoB-100 secretion and bile acid synthesis by HepG2 cells. The principal observations were that: 1) ApoB-100 secretion into the medium was significantly less after the addition of any of the three agents. 2) Triglyceride mass was not significantly changed from control in the medium but was significantly, although modestly, reduced in the cells. 3) Neither free cholesterol (FC) nor cholesteryl ester (CE) mass in the medium was changed; by contrast, CE mass was reduced within the cells although FC was not. 4) Although the total mass of cholesterol in the medium was unaffected, the proportion associated with apoB-100 was reduced, whereas the proportion associated with the non-apoB-100 fraction was increased. 5) There was also an unanticipated, but substantial, increase in bile acid synthesis induced by apoA-I, HDL3, or hydroxy-beta-cyclodextrin, which was time and concentration dependent, and which was associated with marked increases in cholesterol 7 alpha-hydroxylase activity. There were no significant changes in ACAT activity and only modest increases in HMG-CoA reductase activity. These findings support previous clinical observations that an elevated apoB-100 can accompany a low HDL cholesterol in normotriglyceridemic subjects. They also point to physiologically important, although still only partially understood, metabolic relationships amongst hepatic apoB-100 secretion, cholesterol efflux, and bile acid synthesis.
Sniderman
Allan D
AD
Mike Rosenbloom Laboratories for Cardiovascular Research, Cardiovascular Genetics Laboratory, McGill University, Montreal, Canada. allan.sniderman@muhc.mcgill.ca
Zhang
ZuJun
Z
Genest
Jacques
J
Cianflone
Katherine
K
D016632:Apolipoprotein A-I / Q000494:pharmacology; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D003505:Cyclodextrins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology; D053440:Lipoproteins, HDL3; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001647:Bile Acids and Salts; D002788:Cholesterol Esters; D003505:Cyclodextrins; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D002784:Cholesterol