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Updated: Jul 8, 2026
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
Hypocholesterolemic effects of fatty acid bile acid conjugates (FABACs) in mice
Alicia Leikin-Frenkel1, Paolo Parini, Fred M Konikoff
1Minerva Center for Cholesterol Gallstones and Lipid Metabolism in the Liver, Tel-Aviv University, Israel.
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.
Insights
Fatty acid bile acid conjugates (FABACs) significantly lower high cholesterol levels in mice. These compounds reduce cholesterol synthesis while increasing its excretion, offering a potential therapeutic approach.
Area of Science:
- Biochemistry
- Pharmacology
- Hepatology
Background:
- Fatty acid bile acid conjugates (FABACs) are known to prevent cholesterol gallstones and fatty liver in mice.
- Elevated plasma cholesterol is a significant risk factor for cardiovascular diseases.
Purpose of the Study:
- To investigate the hypocholesterolemic effects of FABACs in mice.
- To determine the impact of a specific FABAC, the conjugate of cholic acid with arachidic acid (Aramchol), on plasma and hepatic cholesterol levels.
Main Methods:
- Administration of Aramchol to C57L/J mice on regular (RD) or high-fat diets (HFD).
- Measurement of plasma cholesterol levels.
- Assessment of hepatic cholesterol synthesis and CYP7A1 activity/expression.
- Analysis of fecal bile acid and neutral sterol excretion.
Main Results:
- Aramchol significantly reduced HFD-induced elevated plasma cholesterol by 50% in C57L/J mice.
- Hepatic cholesterol synthesis was decreased, while CYP7A1 activity and expression were increased by Aramchol.
- The ratio of fecal bile acids to neutral sterols increased, alongside elevated total fecal sterol excretion.
Conclusions:
- FABACs, specifically Aramchol, demonstrate potent hypocholesterolemic effects in mice.
- The mechanism involves reduced hepatic cholesterol synthesis and enhanced cholesterol catabolism and excretion.
- FABACs represent a promising therapeutic strategy for managing hypercholesterolemia.
