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

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.

• Authors: Laura E Johnson, Marc S Elias, David T Bolick, Marcus D Skaflen, Richard M Green, Catherine C Hedrick
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 48 Issue 4 Pg. 1138-48 (Oct 2008) ISSN: 1527-3350 [Electronic] United States
• PMID: 18821587 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Bile Acids and Salts
• Cell Cycle Proteins
• DNA-Binding Proteins
• G2A receptor
• Liver X Receptors
• Orphan Nuclear Receptors
• Phospholipids
• Receptors, Cytoplasmic and Nuclear
• Receptors, G-Protein-Coupled
• Transcription Factors
• farnesoid X-activated receptor
• Cholesterol

Topics

• Animals
• Bile Acids and Salts (metabolism)
• Cell Cycle Proteins (genetics, metabolism)
• Cholesterol (metabolism)
• DNA-Binding Proteins (metabolism)
• Diet (adverse effects)
• Disease Models, Animal
• Female
• Gallstones (chemically induced, genetics, metabolism)
• Homeostasis (physiology)
• Lipid Metabolism (genetics, physiology)
• Liver (metabolism)
• Liver X Receptors
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Orphan Nuclear Receptors
• Phospholipids (metabolism)
• Receptors, Cytoplasmic and Nuclear (metabolism)
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Transcription Factors (metabolism)