New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism.
Plant sterols and stanols (phytosterols/phytostanols) are known to reduce serum low-density lipoprotein (LDL)-cholesterol level, and food products containing these plant compounds are widely used as a therapeutic dietary option to reduce plasma cholesterol and atherosclerotic risk. The cholesterol-lowering action of phytosterols/phytostanols is thought to occur, at least in part, through competition with dietary and biliary cholesterol for intestinal absorption in mixed micelles. However, recent evidence suggests that phytosterols/phytostanols may regulate proteins implicated in cholesterol metabolism both in enterocytes and hepatocytes. Important advances in the understanding of intestinal sterol absorption have provided potential molecular targets of phytosterols. An increased activity of ATP-binding cassette transporter A1 (ABCA1) and ABCG5/G8 heterodimer has been proposed as a mechanism underlying the hypocholesterolaemic effect of phytosterols. Conclusive studies using ABCA1 and ABCG5/G8-deficient mice have demonstrated that the phytosterol-mediated inhibition of intestinal cholesterol absorption is independent of these ATP-binding cassette (ABC) transporters. Other reports have proposed a phytosterol/phytostanol action on cholesterol esterification and lipoprotein assembly, cholesterol synthesis and apolipoprotein (apo) B100-containing lipoprotein removal. The accumulation of phytosterols in ABCG5/G8-deficient mice, which develop features of human sitosterolaemia, disrupts cholesterol homeostasis by affecting sterol regulatory element-binding protein (SREBP)-2 processing and liver X receptor (LXR) regulatory pathways. This article reviews the progress to date in studying these effects of phytosterols/phytostanols and the molecular mechanisms involved.
Calpe-Berdiel
Laura
L
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Escolà-Gil
Joan Carles
JC
Blanco-Vaca
Francisco
F
D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry; D000042:Absorption; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D019281:Dimerization; D006706:Homeostasis; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D008956:Models, Chemical; D010840:Phytosterols / Q000378:metabolism*; D012855:Sitosterols / Q000378:metabolism
C577836:ABCA1 protein, human; C416945:ABCG5 protein, human; D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D008078:Cholesterol, LDL; D008074:Lipoproteins; D010840:Phytosterols; D012855:Sitosterols; D002784:Cholesterol