Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption.
The hypocholesterolemic effect of plant stanols is explained by a decreased intestinal cholesterol absorption due to a competition between plant stanols and cholesterol for incorporation into mixed micelles. Earlier we had suggested that plant stanols have a so far unknown action inside the enterocytes. The recent discovery of the involvement of ATP binding cassette (ABC) transporters in cholesterol absorption was a lead to further explore the hypocholesterolemic mechanism of plant stanols. We found that mixed micelles enriched with sitostanol or with cholesterol plus sitostanol were potent inducers of ABCA1 expression in caco-2 cells, an accepted model to study human intestinal lipoprotein metabolism. Based on these findings, we now hypothesize that plant stanols--and possibly plant sterols--increase ABCA1-mediated cholesterol efflux back into the intestinal lumen. We further hypothesize that intracellular levels of plant stanols are monitored by the same sensors (SREBP-2 and LXR) as those that monitor cholesterol. Consequently, increased plant stanol levels within the enterocyte activate cholesterol efflux through ABCA1- but not SREBP-2-mediated endogenous cholesterol synthesis even if intracellular cholesterol concentrations are lowered through consumption of plant stanols. If our hypothesis is correct, then the LXR pathway may be a target for dietary regulation of intestinal lipid metabolism.
Plat
Jogchum
J
Department of Human Biology, Maastricht University, Maastricht, Netherlands. J.Plat@HB.UNIMAAS.NL
Mensink
Ronald P
RP
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D002784:Cholesterol / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008823:Micelles; D008954:Models, Biological; D012333:RNA, Messenger / Q000096:biosynthesis; D012855:Sitosterols / Q000494:pharmacology*
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D008823:Micelles; D012333:RNA, Messenger; D012855:Sitosterols; D002784:Cholesterol; C021255:stigmastanol