title: Reduced biliary sterol output with no change in total faecal excretion in mice expressing a human apolipoprotein A-I variant.
abstract: OBJECTIVE
  Apolipoprotein (apo)A-I(M) (ilano), is a molecular variant of apoA-I(wild-type), associated with dramatically low HDL-cholesterol levels, but no increased risk for cardiovascular disease. In view of the present uncertainties on the role of apoA-I in liver cholesterol removal by way of bile acids and neutral sterols, and of the greater capacity of apoA-I(M) (ilano) to remove arterial cholesterol, biliary sterol metabolism was evaluated in transgenic mice expressing apoA-I(M) (ilano).
  
  
  METHODS
  ApoA-I(M) (ilano) mice were fed a high-cholesterol/high-fat diet, and compared with human apoA-I(wild-type) mice. Plasma lipid levels, hepatic bile flow and composition, hepatic and intestinal cholesterol and bile acid content, and faecal sterol content were measured. Moreover, the expression of hepatic ABCA1, SR-B1 and that of hepatic and intestinal genes involved in bile acid metabolism were evaluated.
  
  
  RESULTS
  The dietary treatment led to a strong elevation in HDL-cholesterol levels in A-I(M) (ilano) mice, associated with an increased expression of hepatic ABCA1. ApoA-I(M) (ilano) mice showed lower cholesterol output from the liver compared with apoA-I(wild-type) mice, in the absence of liver sterol accumulation. Faecal excretion of neutral sterols and bile acids was similar in the two mouse lines.
  
  
  CONCLUSIONS
  In spite of a different response to the dietary challenge, with an increased ABCA1 expression and a lower hepatic cholesterol output in apoA-I(M) (ilano) mice, the net sterol excretion is comparable in the two transgenic lines.
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors: Cinzia
authors: C
authors: Parolini
authors: Silvia
authors: S
authors: Caligari
authors: Donatella
authors: D
authors: Gilio
authors: Stefano
authors: S
authors: Manzini
authors: Marco
authors: M
authors: Busnelli
authors: Marco
authors: M
authors: Montagnani
authors: Marcello
authors: M
authors: Locatelli
authors: Erika
authors: E
authors: Diani
authors: Flavio
authors: F
authors: Giavarini
authors: Donatella
authors: D
authors: Caruso
authors: Enrico
authors: E
authors: Roda
authors: Aldo
authors: A
authors: Roda
authors: Cesare R
authors: CR
authors: Sirtori
authors: Giulia
authors: G
authors: Chiesa
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D005766:Gastrointestinal Contents / Q000737:chemistry; D020869:Gene Expression Profiling; D006801:Humans; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D023421:Models, Animal; D051122:Scavenger Receptors, Class B / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B