Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis

被引:1552
作者
Sinal, CJ
Tohkin, M
Miyata, M
Ward, JM
Lambert, G
Gonzalez, FJ
机构
[1] NIH, Lab Metab, Div Basic Sci, Bethesda, MD 20892 USA
[2] NCI, Vet & Tumor Pathol Sect, Off Lab Anim Sci, NIH, Frederick, MD 21702 USA
[3] NHLBI, Metab Dis Branch, NIH, Bethesda, MD 20892 USA
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0092-8674(00)00062-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mice lacking the nuclear bile acid receptor FXR/BAR developed normally and were outwardly identical to wild-type littermates. RXR/BAR null mice were distinguished from wild-type mice by elevated serum bile acid, cholesterol, and triglycerides, increased hepatic cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. FXR/BAR null mice also had reduced bile acid pools and reduced fecal bile acid excretion due to decreased expression of the major hepatic canalicular bile acid transport protein. Bile acid repression and induction of cholesterol 7 alpha-hydroxylase and the ileal bile acid binding protein, respectively, did not occur in FXR/BAR null mice, establishing the regulatory role of FXR/BAR for the expression of these genes in vivo. These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor.
引用
收藏
页码:731 / 744
页数:14
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