| First Author | Xie Y | Year | 2009 |
| Journal | J Lipid Res | Volume | 50 |
| Issue | 5 | Pages | 977-87 |
| PubMed ID | 19136665 | Mgi Jnum | J:149641 |
| Mgi Id | MGI:3848782 | Doi | 10.1194/jlr.M800645-JLR200 |
| Citation | Xie Y, et al. (2009) Increased susceptibility to diet-induced gallstones in liver fatty acid binding protein knockout mice. J Lipid Res 50(5):977-87 |
| abstractText | Quantitative trait mapping identified a locus colocalizing with L-Fabp, encoding liver fatty acid binding protein, as a positional candidate for murine gallstone susceptibility. When fed a lithogenic diet (LD) for 2 weeks, L-Fabp(-/-) mice became hypercholesterolemic with increased hepatic VLDL cholesterol secretion. Seventy-five percent of L-Fabp(-/-) mice developed solid gallstones compared with 6% of wild-type mice with an increased gallstone score (3.29 versus 0.62, respectively; P < 0.01). Hepatic free cholesterol content, biliary cholesterol secretion, and the cholesterol saturation index of hepatic bile were increased in LD-fed L-Fabp(-/-) mice. Chow-fed L-Fabp(-/-) mice demonstrated increased fecal bile acid (BA) excretion accompanied by decreased ileal Asbt expression. By contrast, there was an increased BA pool and decreased fecal BA excretion in LD-fed L-Fabp(-/-) mice, associated with increased proximal intestinal Asbt mRNA expression, suggesting that intestinal BA absorption was enhanced in LD-fed L-Fabp(-/-) mice. The increase in biliary BA secretion and enterohepatic pool size in LD-fed L-Fabp(-/-) mice was accompanied by downregulation of Cyp7a1 mRNA and increased intestinal mRNA abundance of Fgf-15, Fxr, and Fabp6. These findings suggest that changes in hepatic cholesterol metabolism and biliary lipid secretion as well as changes in enterohepatic BA metabolism increase gallstone susceptibility in LD fed L-Fabp(-/-) mice. |
