| Disodium ascorbyl phytostanol phosphate (FM-VP4), a modified phytostanol, is a highly active hypocholesterolaemic agent that affects the enterohepatic circulation of both cholesterol and bile acids in mice. | |
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MedLine Citation:
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PMID: 19822032 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Disodium ascorbyl phytostanol phosphate (FM-VP4) is a synthetic compound derived from sitostanol and campestanol that has proved to be efficient as a cholesterol-lowering therapy in mice and human subjects. However, the mechanism of action of FM-VP4 remains unknown. The present study tests the ability of FM-VP4 to alter intestinal and liver cholesterol homeostasis in mice. Female C57BL/6J mice were fed either a control chow or a 2 % FM-VP4-enriched diet for 4 weeks. FM-VP4 reduced the in vivo net intestinal cholesterol absorption and plasma and liver cholesterol concentrations by 2.2-, 1.5- and 1.6-fold, respectively, compared with control mice. Furthermore, FM-VP4 also showed an impact on bile acid homeostasis. In FM-VP4 mice, liver and intestinal bile acid content was increased by 1.3- and 2.3-fold, respectively, whereas faecal bile acid output was 3.3-fold lower. FM-VP4 also increased the intestinal absorption of orally administered [3H]taurocholic acid to small intestine in vivo. Inhibition of intestinal cholesterol absorption by FM-VP4 was not mediated via transcriptional increases in intestine liver X receptor (LXR)-alpha, adenosine triphosphate-binding cassette transporter (ABC)-A1, ABCG5/G8 nor to decreases in intestinal Niemann-Pick C1-like 1 (NPC1L1) expression. In contrast, FM-VP4 up-regulated liver LXRalpha, ABCA1, ABCG5, scavenger receptor class BI (SR-BI) and hydroxymethylglutaryl coenzyme A reductase (HMGCoA-R) gene expression, whereas it down-regulated several farnesoid X receptor (FXR)-target genes such as cytochrome P450 family 7 subfamily A polypeptide 1 (CYP7A1) and Na+/taurocholate co-transporter polypeptide (NTCP). In conclusion, FM-VP4 reduced intestinal cholesterol absorption, plasma and liver cholesterol and affected bile acid homeostasis by inducing bile acid intestinal reabsorption and changed the liver expression of genes that play an essential role in cholesterol homeostasis. This is the first phytosterol or stanol that affects bile acid metabolism and lowers plasma cholesterol levels in normocholesterolaemic mice. |
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Authors:
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J Méndez-González; S Süren-Castillo; L Calpe-Berdiel; N Rotllan; M Vázquez-Carrera; J C Escolà-Gil; F Blanco-Vaca |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-13 |
Journal Detail:
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Title: The British journal of nutrition Volume: 103 ISSN: 1475-2662 ISO Abbreviation: Br. J. Nutr. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-24 Completed Date: 2010-02-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372547 Medline TA: Br J Nutr Country: England |
Other Details:
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Languages: eng Pagination: 153-60 Citation Subset: IM |
Affiliation:
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Servei de Bioquímica and Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile Acids and Salts / blood, secretion Body Weight / drug effects Cholesterol / blood, metabolism Energy Intake Humans Intestinal Absorption / drug effects Intestine, Small / drug effects, physiology Liver / drug effects, physiology Liver Circulation / drug effects*, physiology Male Mice Mice, Inbred C57BL Phytosterols / pharmacology* RNA / genetics, isolation & purification Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Bile Acids and Salts; 0/FM-VP4 compound; 0/Phytosterols; 57-88-5/Cholesterol; 63231-63-0/RNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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