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.
Gilat
Tuvia
T
Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Israel.
Leikin-Frenkel
Alicia
A
Goldiner
Ilana
I
Juhel
Christine
C
Lafont
Huguette
H
Gobbi
Diana
D
Konikoff
Fred M
FM
D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001835:Body Weight; D002793:Cholic Acids; D006224:Cricetinae; D004041:Dietary Fats / Q000493:pharmacokinetics; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000493:pharmacokinetics; D014304:Triolein / Q000493:pharmacokinetics; D014316:Tritium
D001647:Bile Acids and Salts; D002793:Cholic Acids; D004041:Dietary Fats; D014280:Triglycerides; D014316:Tritium; D014304:Triolein; C455117:aramchol