Vassileva Galya, Golovko Andrei, Markowitz Lisa, Abbondanzo Susan J, Zeng Ming, Yang Shijun, Hoos Lizbeth, Tetzloff Glen, Levitan Diane, Murgolo Nicholas J, Keane Kevin, Davis Harry R, Hedrick Joseph, Gustafson Eric L
Department of Discovery Technologies, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Biochem J. 2006 Sep 15;398(3):423-30. doi: 10.1042/BJ20060537.
The Gpbar1 [G-protein-coupled BA (bile acid) receptor 1] is a recently identified cell-surface receptor that can bind and is activated by BAs, but its physiological role is unclear. Using targeted deletion of the Gpbar1 gene in mice, we show that the gene plays a critical role in the maintenance of bile lipid homoeostasis. Mice lacking Gpbar1 expression were viable, developed normally and did not show significant difference in the levels of cholesterol, BAs or any other bile constituents. However, they did not form cholesterol gallstones when fed a cholic acid-containing high-fat diet, and liver-specific gene expression indicated that Gpbar1-deficient mice have altered feedback regulation of BA synthesis. These results suggest that Gpbar1 plays a critical role in the formation of gallstones, possibly via a regulatory mechanism involving the cholesterol 7alpha-hydroxylase pathway.
Gpbar1 [G蛋白偶联胆汁酸（BA）受体1] 是最近发现的一种细胞表面受体，它能够结合胆汁酸并被其激活，但其生理作用尚不清楚。通过对小鼠Gpbar1基因进行靶向缺失，我们发现该基因在维持胆汁脂质稳态中起关键作用。缺乏Gpbar1表达的小鼠能够存活，发育正常，胆固醇、胆汁酸或任何其他胆汁成分的水平均无显著差异。然而，当喂食含胆酸的高脂饮食时，它们不会形成胆固醇胆结石，肝脏特异性基因表达表明，Gpbar1基因缺陷型小鼠的胆汁酸合成反馈调节发生了改变。这些结果表明，Gpbar1可能通过涉及胆固醇7α-羟化酶途径的调节机制在胆结石形成中起关键作用。
