The G protein-coupled receptor G2A: Involvement in hepatic lipid metabolism and gallstone formation in mice

Laura E. Johnson, Marc S. Elias, David T. Bolick, Marcus D. Skaflen, Richard M. Green, Catherine C. Hedrick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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 7α-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.

Original languageEnglish (US)
Pages (from-to)1138-1148
Number of pages11
JournalHepatology
Volume48
Issue number4
DOIs
StatePublished - Oct 2008

ASJC Scopus subject areas

  • Hepatology

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