title: A reappraisal of the mechanism by which plant sterols promote neutral sterol loss in mice.
abstract: Dietary plant sterols (PS) reduce serum total and LDL-cholesterol in hyperlipidemic animal models and in humans. This hypocholesterolemic effect is generally ascribed to inhibition of cholesterol absorption. However, whether this effect fully explains the reported strong induction of neutral sterol excretion upon plant sterol feeding is not known. Recent data demonstrate that the intestine directly mediates plasma cholesterol excretion into feces, i.e., without involvement of the hepato-biliary route.
  
  
  OBJECTIVE
  Aim of this study was to determine whether stimulation of fecal neutral sterol loss during PS feeding is (partly) explained by increased intestinal cholesterol excretion and to assess the role of the cholesterol transporter Abcg5/Abcg8 herein.
  
  
  RESULTS
  Wild-type mice were fed a control diet or diets enriched with increasing amounts of PS (1%, 2%, 4% or 8%, wt/wt) for two weeks. In addition, Abcg5(-/-) mice were fed either control or 8% PS diet. PS feeding resulted in a dose-dependent decrease of fractional cholesterol absorption (∼2-7-fold reduction) in wild-type mice and ∼80% reduction in Abcg5(-/-) mice. Furthermore, PS feeding led to a strong, dose-independent induction of neutral sterol excretion (3.4-fold in wild-types and 2.7-fold in Abcg5(-/-) mice) without changes in biliary cholesterol secretion. It was calculated that PS feeding stimulated intestinal cholesterol excretion by ∼500% in wild-type mice and by ∼250% in Abcg5(-/-).
  
  
  CONCLUSIONS
  Our data indicate that in mice the cholesterol-lowering effects of PS are to a large extent attributable to stimulation of intestinal, non-bile derived, cholesterol excretion. The Abcg5/Abcg8 heterodimer is involved in facilitating this PS-induced flux of cholesterol.
authors: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. g.brufau.dones@med.umcg.nl
authors: Gemma
authors: G
authors: Brufau
authors: Folkert
authors: F
authors: Kuipers
authors: Yuguang
authors: Y
authors: Lin
authors: Elke A
authors: EA
authors: Trautwein
authors: Albert K
authors: AK
authors: Groen
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002784:Cholesterol / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010840:Phytosterols / Q000494:pharmacology*; D016133:Polymerase Chain Reaction
chemical_list: C462600:ABCG5 protein, mouse; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D008074:Lipoproteins; D010840:Phytosterols; D002784:Cholesterol