ArticleHepatology (Baltimore, Md.)2016
Evidence that the adenosine triphosphate-binding cassette G5/G8-independent pathway plays a determinant role in cholesterol gallstone formation in mice.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 25 citations in OpenAlex.
- A Gallbladder-Specific Hydrophobic Bile Acid-FXR-MUC1 Signaling Axis Mediates Cholesterol Gallstone Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Sodium butyrate activates peroxisome proliferator-activated receptor γ to suppress lithogenic diet-induced cholesterol gallstones in mice.Food science and biotechnology · 2025Article
- Macrophage inhibitory cytokine-1 aggravates diet-induced gallstone formation via increased ABCG5/ABCG8 expression.PloS one · 2023Article
- Sitosterolemia: Twenty Years of Discovery of the Function ofInternational journal of molecular sciences · 2021Review
- miRNA-223 Suppresses Mouse Gallstone Formation by Targeting Key Transporters in Hepatobiliary Cholesterol Secretion Pathway.International journal of biological sciences · 2021Article
- The effect of ursodeoxycholic acid on the relative expression of the lipid metabolism genes in mouse cholesterol gallstone models.Lipids in health and disease · 2020Article
- A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice.Journal of lipid research · 2020Article
- Recent Advances in the Critical Role of the Sterol Efflux Transporters ABCG5/G8 in Health and Disease.Advances in experimental medicine and biology · 2020Review
- Role of Baicalin and Liver X Receptor Alpha in the Formation of Cholesterol Gallstones in Mice.Gastroenterology research and practice · 2020Article
- Distribution of the ATP-binding cassette transporter ABCG8 IVS1-2A>G genotype and clinical characteristics of gallbladder patients in Northeastern Mexico: A pilot study.Biomedical reports · 2018Article
- ABCG5 and ABCG8: more than a defense against xenosterols.Journal of lipid research · 2018Review
- Mouse models of gallstone disease.Current opinion in gastroenterology · 2018Review
- Article
- New insights into the role ofLiver research (Beijing, China) · 2017Article
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Abstract
unlabelledThe adenosine triphosphate-binding cassette (ABC) sterol transporter, Abcg5/g8, is Lith9 in mice, and two gallstone-associated variants in ABCG5/G8 have been identified in humans. Although ABCG5/G8 plays a critical role in determining hepatic sterol secretion, cholesterol is still secreted to bile in sitosterolemic patients with a defect in either ABCG5 or ABCG8 and in either Abcg5/g8 double- or single-knockout mice. We hypothesize that in the defect of ABCG5/G8, an ABCG5/G8-independent pathway is essential for regulating hepatic secretion of biliary sterols, which is independent of the lithogenic mechanism of the ABCG5/G8 pathway. To elucidate the effect of the ABCG5/G8-independent pathway on cholelithogenesis, we investigated the biliary and gallstone characteristics in male wild-type (WT), ABCG5(-/-)/G8(-/-), and ABCG8 (-/-) mice fed a lithogenic diet or varying amounts of cholesterol, treated with a liver X receptor (LXR) agonist, or injected intravenously with [(3) H]sitostanol- and [(14) C]cholesterol-labeled high-density lipoprotein (HDL). We found that ABCG5(-/-)/G8(-/-) and ABCG8 (-/-) mice displayed the same biliary and gallstone phenotypes. Although both groups of knockout mice showed a significant reduction in hepatic cholesterol output compared to WT mice, they still formed gallstones. The LXR agonist significantly increased biliary cholesterol secretion and gallstones in WT, but not ABCG5(-/-)/G8(-/-) or ABCG8 (-/-), mice. The 6-hour recovery of [(14) C]cholesterol in hepatic bile was significantly lower in both groups of knockout mice than in WT mice and [(3) H]sitostanol was detected in WT, but not ABCG5(-/-)/G8(-/-) or ABCG8 (-/-), mice.
conclusionsThe ABCG5/G8-independent pathway plays an important role in regulating biliary cholesterol secretion, the transport of HDL-derived cholesterol from plasma to bile, and gallstone formation, which works independently of the ABCG5/G8 pathway. Further studies are needed to observe whether this pathway is also operational in humans. (Hepatology 2016;64:853-864).
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