文章基本信息

标题：Increased susceptibility to diet-induced gallstones in liver fatty acid binding protein knockout mice
本地全文：下载
作者：Yan Xie ; Elizabeth P. Newberry ; Susan M. Kennedy 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2009
卷号：50
期号：5
页码：977-987
DOI：10.1194/jlr.M800645-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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 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.