ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Conjugated Lithocholic Acid Activates Hepatic TGR5 to Promote Lipotoxicity and MASLD-MASH Transition by Disrupting Carnitine Biosynthesis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- A functional genomics-pharmacotranscriptomics framework identifies host-directed anti-influenza agents.iScience · 2026Article
- Gut Microbiota, Immunity, and Metabolism in the Progression From Chronic Liver Disease to Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Microbiota-Driven Metabolic Alterations Induced by BPA, TDCPP and PFOA in an Ex Vivo Human Fecal Fermentation Model.Chemical research in toxicology · 2026Article
- Gut microbiome and bile acid metabolism in liver disease: Mechanisms, clinical implications, and therapeutic opportunities.Pharmacological reviews · 2026Review
- Dysregulation of the AMPK-SREBP1-FASN axis in MASLD: driving a vicious cycle of lipotoxicity and metabolic-immune crosstalk.Lipids in health and disease · 2026Review
- Inhibiting TRIM21 Neddylation Rejuvenates Oocyte Quality in PCOS by Regulating Ubiquitination of CPT1A.Research (Washington, D.C.) · 2026Article
- Bile acid-axis dysregulation in MASLD/MASH progression: from metabolic mismatch to inflammatory-fibrotic remodeling.Frontiers in medicine · 2026Review
- The role of bile acid-activated receptor TGR5 in inflammation and liver diseases.Frontiers in physiology · 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
- Gut microbial metabolites in cancer immunomodulation.Molecular cancer · 2025Review
- Microbiome-derived bile acids as endogenous regenerative mediators in liver repair.Regenerative therapy · 2025Review
- Lithocholic Acid Species: Metabolism, Signaling Pathways, and Clinical Significance in Enterohepatic Diseases.International journal of molecular sciences · 2025Review
- Microbial changes resulting from VSG attenuate MASLD by modulating bile acid metabolism and the intestinal FXR-FGF19 axis.mSystems · 2025Article
- Conjugated Lithocholic Acid Activates Hepatic TGR5 to Promote Lipotoxicity and MASLD-MASH Transition by Disrupting Carnitine Biosynthesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Immune Microenvironment on the Molecular Mechanisms and Therapeutic Targets of MAFLD.ImmunoTargets and therapy · 2025Review
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Authors and funding
11 authors.
Funding
Abstract
Conjugated lithocholic acid (LCA) plays a critical role in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). In this process, hepatocyte inflammation-caused upregulation of its receptor, Takeda G protein-coupled receptor 5 (TGR5) is a crucial factor. Serum bile acid profiling shows an increase in conjugated LCA, which correlates with disease severity. Depletion of Gpbar1 in hepatocytes significantly protects against the progression from MASLD to metabolic dysfunction-associated steatohepatitis (MASH) that is related to conjugated LCA. In vivo and in vitro experiments indicate that TGR5 activation in hepatocytes promotes lipotoxicity-induced cell death and inflammation by suppressing de novo carnitine biosynthesis. Mechanistically, TGR5 binding to CD36 facilitates E3 ubiquitin ligase TRIM21 recruitment, leading to the degradation of BBOX1, a crucial enzyme in de novo carnitine biosynthesis. Targeting TGR5 therapeutically can restore carnitine biosynthesis, which may offer a potent strategy to prevent or reverse the transition from MASLD to MASH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.