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New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism

  • Laura Calpe-Berdiel
    Affiliations
    Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Barcelona. Spain
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  • Joan Carles Escolà-Gil
    Correspondence
    Corresponding author at: Hospital de la Santa Creu i Sant Pau, Servei de Bioquímica, C/ Antoni M. Claret 167, 08025 Barcelona, Spain. Tel.: +34 93 2919261; fax: +34 93 2919196.
    Affiliations
    Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Barcelona. Spain

    CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Spain
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  • Francisco Blanco-Vaca
    Affiliations
    Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Spain

    Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
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      Abstract

      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.

      Abbreviations:

      ACAT (acyl-CoA:cholesterol acyltransferase), ABC (adenosine triphosphate-binding cassette transporter), ANXA2–CAV1 (annexin 2/caveolin 1), apo (apolipoprotein), CVD (cardiovascular disease), CYP7A1 (cytochrome P450 family 7 subfamily A polypeptide 1), FPPS (farnesyl pyrophosphate synthase), FC (free cholesterol), HDL (high-density lipoprotein), HMG-CoA (hydroxymethylglutaryl coenzyme A), IDL (intermediate-density lipoprotein), LXR (liver X receptor), LDL (low-density lipoprotein), LDLr (LDL receptor), LRP (LDL-related protein), NPC1L1 (Niemann-Pick C1-like 1), PPAR (peroxisome-proliferator-activated receptor), RXR (retinoid X receptor), SR-BI (scavenger receptor class-BI), SREBP (sterol regulatory element-binding protein), VLDL (very low-density lipoprotein)

      Keywords

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