Hypocholesterolemic effects of fatty acid bile acid conjugates (FABACs) in mice.
Fatty acid bile acid conjugates (FABACs) prevent and dissolve cholesterol gallstones and prevent diet induced fatty liver, in mice. The present studies aimed to test their hypocholesterolemic effects in mice. Gallstone susceptible (C57L/J) mice, on high fat (HFD) or regular diet (RD), were treated with the conjugate of cholic acid with arachidic acid (FABAC; Aramchol). FABAC reduced the elevated plasma cholesterol levels induced by the HFD. In C57L/J mice, FABAC reduced plasma cholesterol by 50% (p<0.001). In mice fed HFD, hepatic cholesterol synthesis was reduced, whereas CYP7A1 activity and expression were increased by FABAC. The ratio of fecal bile acids/neutral sterols was increased, as was the total fecal sterol excretion. In conclusion, FABACs markedly reduce elevated plasma cholesterol in mice by reducing the hepatic synthesis of cholesterol, in conjunction with an increase of its catabolism and excretion from the body.
Leikin-Frenkel
Alicia
A
Minerva Center for Cholesterol Gallstones and Lipid Metabolism in the Liver, Tel-Aviv University, Israel.
Parini
Paolo
P
Konikoff
Fred M
FM
Benthin
Lisbet
L
Leikin-Gobbi
Diana
D
Goldiner
Ilana
I
Einarsson
Curt
C
Gilat
Tuvia
T
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000008:administration & dosage* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D002793:Cholic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D004041:Dietary Fats / Q000008:administration & dosage; D004537:Eicosanoic Acids / Q000008:administration & dosage; D005243:Feces / Q000737:chemistry; D042882:Gallstones / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D020022:Genetic Predisposition to Disease; D008074:Lipoproteins / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002793:Cholic Acids; D004041:Dietary Fats; D004537:Eicosanoic Acids; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; C094477:arachidic acid; C455117:aramchol