ArticleThe Journal of clinical investigation2014
Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01129297 (Influence of the Glycemic and Ponderal Status on Tissues Gene Expression), which is not on this map. Cited by 78 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Influence of the Glycemic and Ponderal Status on Tissues Gene Expression (Biological Tissue Collection)
Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Meta-analysis and Consolidation of Farnesoid X Receptor Chromatin Immunoprecipitation Sequencing Data Across Different Species and Conditions.Hepatology communications · 2021Pooled it
- Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment.Nature communications · 2017Trial
- Scalable synthetic peptide hydrogel enables self-organized luminal cavity architecture within hiPSC 3D colonies supporting functional hepatocyte differentiation.Bioactive materials · 2026Article
- The eternal struggle between titans: Fecal microbiota transplant (FMT) versus metformin in type 2 diabetes (T2D) gut dysmotility.Journal of advanced research · 2026Review
- Epigenetic regulation and posttranslational modifications of FXR: underlying mechanisms and implications in digestive diseases.Acta pharmacologica Sinica · 2026Review
- Pharmacomicrobiomics of Non-Antibiotic Drugs: Mechanisms and Clinical Consequences of Gut Microbiota Alterations.Pharmaceutics · 2026Review
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Declining FXR expression coordinates neonatal beta cell mass development with microbial bile acid metabolism maturation in mice.Diabetologia · 2026Article
- Aging-driven metabolic abnormalities remodel intercellular communication through the gut-liver-heart axis and may promote coronary artery disease: the key role of bile acid metabolism.Frontiers in immunology · 2026Review
- IMM-H007 promotes hepatic cholesterol and triglyceride metabolism by activating AMPKActa pharmaceutica Sinica. B · 2025Article
- Circulating metabolite signatures indicate differential gut-liver crosstalk in lean and obese MASLD.JCI insight · 2025Article
- Disrupting bile acid metabolism by suppressing Fxr causes hepatocellular carcinoma induced by YAP activation.Nature communications · 2025Article
- Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea.Microbiome · 2025Article
- Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.Current medicinal chemistry · 2025Review
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- High-throughput transcriptomics of 409 bacteria-drug pairs reveals drivers of gut microbiota perturbation.Nature microbiology · 2024Article
- Understanding the action mechanisms of metformin in the gastrointestinal tract.Frontiers in pharmacology · 2024Review
- Review
- Pharmacological management of youth with type 2 diabetes and diabetic kidney disease: a comprehensive review of current treatments and future directions.Expert opinion on pharmacotherapy · 2023Review
- Interactions between Intestinal Homeostasis and NADNutrients · 2023Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nuclear bile acid receptor farnesoid X receptor (FXR) is an important transcriptional regulator of bile acid, lipid, and glucose metabolism. FXR is highly expressed in the liver and intestine and controls the synthesis and enterohepatic circulation of bile acids. However, little is known about FXR-associated proteins that contribute to metabolic regulation. Here, we performed a mass spectrometry-based search for FXR-interacting proteins in human hepatoma cells and identified AMPK as a coregulator of FXR. FXR interacted with the nutrient-sensitive kinase AMPK in the cytoplasm of target cells and was phosphorylated in its hinge domain. In cultured human and murine hepatocytes and enterocytes, pharmacological activation of AMPK inhibited FXR transcriptional activity and prevented FXR coactivator recruitment to promoters of FXR-regulated genes. Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine. In a mouse model of intrahepatic cholestasis, metformin treatment induced FXR phosphorylation, perturbed bile acid homeostasis, and worsened liver injury. Together, our data indicate that AMPK directly phosphorylates and regulates FXR transcriptional activity to precipitate liver injury under conditions favoring cholestasis.
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Registered trials
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.