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Prevention of diet‐induced fatty liver in experimental animals by the oral administration of a fatty acid bile acid conjugate (FABAC)

Fatty acid bile acid conjugates (FABACs) are a new family of synthetic molecules designed to solubilize biliary cholesterol. They were shown to prevent and dissolve cholesterol gallstones in inbred C57L/J mice fed a lithogenic, high‐fat diet (HFD). In these mice, fatty liver was observed in the controls but not in the FABAC‐treated ones. The present study was designed to study the effect of FABAC (arachidyl‐amido‐cholanoic acid) on diet‐induced fatty liver in rats, hamsters, and mice. The fatty liver score (on a scale of 0‐4 by light microscopy) was 4.0 in control hamsters and 0.3 in the FABAC‐fed hamsters (P < .001). In mice it was 1.5 and 0.4, respectively (P < .01). The lipid/protein ratio in the liver was 1.3 ± 0.44 (mg lipid/mg protein) in control rats and 0.66 ± 0.04 in the FABAC group (P = .001) after 14 days. In hamsters it was 1.41 ± 0.27 and 1.11 ± 0.20, respectively (P = .03), after 21 days. In Imperial Charles River (ICR) mice the ratio was 0.34 ± 0.10 and 0.17 ± 0.07 (P = .03), respectively, after 24 days. Liver fat concentration, measured as mg lipid/g liver tissue, decreased similarly by FABAC feeding. The decrease in liver fat affected mainly the triglyceride levels. FABAC‐fed animals gained weight similarly to the controls. Triglyceride absorption was unaffected by FABAC supplementation. In conclusion, oral FABAC therapy prevents/reduces the development of fatty liver in animals consuming a HFD.