Hypocholesterolemic effects of fatty acid bile acid conjugates (FABACs) in mice |
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Authors: | Leikin-Frenkel Alicia Parini Paolo Konikoff Fred M Benthin Lisbet Leikin-Gobbi Diana Goldiner Ilana Einarsson Curt Gilat Tuvia |
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Affiliation: | a Minerva Center for Cholesterol Gallstones and Lipid Metabolism in the Liver, Tel-Aviv University, Israel b Division of Clinical Chemistry, Department of Laboratory Medicine, C1:74, Karolinska Institutet at Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden c Division of Gastroenterology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden d Department of Gastroenterology, Meir Medical Center, Kfar Saba, Israel e Department of Gastroenterology, Tel-Aviv Sourasky Medical Center, Israel f Galmed Medical Research, Ltd., Tel-Aviv, Israel |
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Abstract: | 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. |
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Keywords: | Cholesterol Bile acid Fatty acid Liver Lipoproteins Neutral sterols Gallstone Mice |
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