The G Protein-coupled Receptor G2A: Involvement in Hepatic Lipid Metabolism and Gallstone Formation in Mice

Overview

Journal Hepatology

Specialty Gastroenterology

Date 2008 Sep 30

PMID 18821587

Citations 9

Authors

Laura E Johnson

Marc S Elias

David T Bolick

Marcus D Skaflen

Richard M Green

Catherine C Hedrick

Affiliations

Soon will be listed here.

Abstract

Unlabelled: The G2A receptor is a member of the ovarian cancer G protein-coupled receptor 1 family of stress-inducible G protein-coupled receptors. In this study, we examined the hepatobiliary effects of loss of function of G2A in mice fed either a chow or lithogenic diet. G2A-deficient (G2A(-/-)) mice fed chow had a 25% reduction in biliary phosphatidylcholine content, reduced hepatic gene expression of the phosphatidylcholine transporter adenosine triphosphate-binding cassette B4, and an 8-fold increase in expression of the nuclear receptor liver X receptor (LXR). Despite the increased expression of LXR, transcription of several LXR target genes was reduced. G2A(-/-) mice fed a lithogenic diet had rapid gallstone formation, an increased cholesterol saturation index, a 2.5-fold increase in farnesoid X receptor expression, a 5-fold increase in LXR expression, and a 90% reduction in cholesterol 7alpha-hydroxylase expression in comparison with wild-type mice. There were no changes in gallbladder volume.

Conclusion: These data demonstrate that the G2A receptor is important for hepatobiliary bile salt, cholesterol, and phospholipid homeostasis and for the pathogenesis of cholesterol gallstone formation.

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