ArticleJHEP reports : innovation in hepatology2021
TGR5 controls bile acid composition and gallbladder function to protect the liver from bile acid overload.
Article in JHEP reports : innovation in hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Gut microbiome drives glycodeoxycholic acid-mediated attenuation of hypertension.Gut microbes · 2026Article
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Article
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- The Gut-Liver Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Mechanisms, Microbiome Interactions and Therapeutic Targets.Probiotics and antimicrobial proteins · 2026Review
- Activation of the TGR5/cAMP/PKA/CREB axis in cholangiocytes mediates epithelial-mesenchymal transition and fibrosis in hepatolithiasis.Biology direct · 2026Article
- Myeloid Fmr1 deficiency in mice results in reduced serum cholesterol and altered bile pathway gene expression.PloS one · 2026Article
- Cholecystectomy-induced gut dysbiosis and its consequences: bridging animal models and clinical outcomes in narrative review.Translational gastroenterology and hepatology · 2026Review
- Research Progress on the Mechanism and Targeted Intervention of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1)-Mediated "Inflammation-Apoptosis-Metabolism-Microcirculation" Regulatory Network in Hepatitis B-Associated Liver Failure.Drug design, development and therapy · 2026Review
- The role of bile acid-activated receptor TGR5 in inflammation and liver diseases.Frontiers in physiology · 2026Review
- Biological functions and pharmacological behaviors of bile acids in metabolic diseases.Journal of advanced research · 2025Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Gut microbiome and inflammation in cardiovascular drug response: trends in therapeutic success and commercial focus.Inflammopharmacology · 2025Review
- GLP-1 receptor agonists and gallbladder disease risk: insights into molecular mechanisms and clinical implications.Therapeutic advances in endocrinology and metabolism · 2025Review
- Takeda G protein-coupled receptor 5 (TGR5): an attractive therapeutic target for aging-related cardiovascular diseases.Frontiers in pharmacology · 2025Review
- Synthesis of TUDCA from chicken bile: immobilized dual-enzymatic system for producing artificial bear bile substitute.Microbial cell factories · 2024Review
- Bile acids and coronavirus disease 2019.Acta pharmaceutica Sinica. B · 2024Review
- Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury.Scientific reports · 2024Article
- Understanding the role of ursodeoxycholic acid and gut microbiome in non-alcoholic fatty liver disease: current evidence and perspectives.Frontiers in pharmacology · 2024Review
- Bile Acid Overload Induced by Bile Duct and Portal Vein Ligation Improves Survival after Staged Hepatectomy in Rats.Current medical science · 2023Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsAs the composition of the bile acid (BA) pool has a major impact on liver pathophysiology, we studied its regulation by the BA receptor Takeda G protein coupled receptor (TGR5), which promotes hepatoprotection against BA overload.
methodsWild-type, total and hepatocyte-specific TGR5-knockout, and TGR5-overexpressing mice were used in: partial (66%) and 89% extended hepatectomies (EHs) upon normal, ursodeoxycholic acid (UDCA)- or cholestyramine (CT)-enriched diet, bile duct ligation (BDL), cholic acid (CA)-enriched diet, and TGR5 agonist (RO) treatments. We thereby studied the impact of TGR5 on: BA composition, liver injury, regeneration and survival. We also performed analyses on the gut microbiota (GM) and gallbladder (GB). Liver BA composition was analysed in patients undergoing major hepatectomy.
resultsThe TGR5-KO hyperhydrophobic BA composition was not directly related to altered BA synthesis, nor to TGR5-KO GM dysbiosis, as supported by hepatocyte-specific KO mice and co-housing experiments, respectively. The TGR5-dependent control of GB dilatation was crucial for BA composition, as determined by experiments including RO treatment and/or cholecystectomy. The poor TGR5-KO post-EH survival rate, related to exacerbated peribiliary necrosis and BA overload, was improved by shifting BAs toward a less toxic composition (CT treatment). After either BDL or a CA-enriched diet with or without cholecystectomy, we found that GB dilatation had strong TGR5-dependent hepatoprotective properties. In patients, a more hydrophobic liver BA composition was correlated with an unfavourable outcome after hepatectomy.
conclusionsBA composition is crucial for hepatoprotection in mice and humans. We indicate TGR5 as a key regulator of BA profile and thereby as a potential hepatoprotective target under BA overload conditions. LAY SUMMARY: Through multiple
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