title: Faecal sterol output is increased by arachidyl amido cholanoic acid (Aramchol) in rats.
abstract: Fatty acid-bile acid conjugates (FABACs) were shown recently to have important and multiple effects on cholesterol metabolism. In human fibroblasts, they were found to markedly enhance cholesterol efflux by an ATP-binding cassette transporter A1-dependent pathway. In C57L/J mice, they increased CYP7A1 activity and RNA expression, while decreasing moderately 3-hydroxy-3-methylglutaryl-CoA reductase activity. In C57L/J mice and in hamsters, they also decreased serum cholesterol levels, whereas in other animals, this effect was not seen in short-term experiments. In the present study, we investigated potential mechanisms of action of arachidyl amido cholanoic acid (Aramchol), with particular reference to biliary and faecal sterol outputs in rats. Supplementation with Aramchol at a dose of 150 mg x kg(-1) x day(-1) increased neutral sterol output by approx. 50%, while the faecal outputs of bile salts and total sterols increased by almost 2-fold. Biliary lipid outputs were not significantly different between the control and FABAC-supplemented animals. These findings indicate an overall catabolic effect of FABACs on body cholesterol.
authors.affiliation: Minerva Center for Cholesterol, Gallstones and Lipid Metabolism in the Liver, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. alicial@post.tau.ac.il
authors.forename: A
authors.initials: A
authors.lastname: Leikin-Frenkel
authors.forename: A A
authors.initials: AA
authors.lastname: Weinbroum
authors.forename: D
authors.initials: D
authors.lastname: Leikin-Gobbi
authors.forename: L
authors.initials: L
authors.lastname: Krupitzky
authors.forename: I
authors.initials: I
authors.lastname: Goldiner
authors.forename: L
authors.initials: L
authors.lastname: Shafat
authors.forename: T
authors.initials: T
authors.lastname: Gilat
authors.forename: F M
authors.initials: FM
authors.lastname: Konikoff
mesh_terms: D000821:Animal Feed; D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000494:pharmacology*; D002793:Cholic Acids; D005243:Feces / Q000737:chemistry*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013261:Sterols / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; D002793:Cholic Acids; D013261:Sterols; C455117:aramchol