期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 10, 页码 3891-3896出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0712328105
关键词
cholesterol; liver disease; mouse model; nuclear receptor
资金
- NCI NIH HHS [CA73728, R01 CA073728, U01 CA073728] Funding Source: Medline
- NIDDK NIH HHS [F32 DK079576, R29 DK047987, DK47987, R01 DK047987] Funding Source: Medline
The apical sodium-dependent bile acid transporter (Asbt) is responsible for transport across the intestinal brush border membrane; however, the carrier(s) responsible for basolateral bile acid export into the portal circulation remains to be determined. Although the heteromeric organic solute transporter Ost alpha-Ost beta exhibits many properties predicted for a candidate intestinal basolateral bile acid transporter, the in vivo functions of Ost alpha-Ost beta have not been investigated. To determine the role of Ost alpha-Ost beta in intestinal bile acid absorption, the Ost alpha gene was disrupted by homologous recombination in mice. Ost alpha(-/-) mice were physically indistinguishable from wild-type mice. In everted gut sac experiments, transileal transport of taurocholate was reduced by >80% in Ost alpha(-/-) vs. wild-type mice; the residual taurocholate transport was further reduced to near-background levels in gut sacs prepared from Ost alpha(-/-)Mrp3(-/-) mice. The bile acid pool size was significantly reduced (>65%) in Ost alpha(-/-) mice, but fecal bile acid excretion was not elevated. The decreased pool size in Ost alpha(-/-) mice resulted from reduced hepatic Cyp7a1 expression that was inversely correlated with ileal expression of fibroblast growth factor 15 (FGF15). These data indicate that Ost alpha-Ost beta is essential for intestinal bile acid transport in mice. Unlike a block in intestinal apical bile acid uptake, genetic ablation of basolateral bile acid export disrupts the classical homeostatic control of hepatic bile acid biosynthesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据