ArticleWorld journal of gastroenterology2014
FXR agonist GW4064 alleviates endotoxin-induced hepatic inflammation by repressing macrophage activation.
Article in World journal of gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 74 citations in OpenAlex.
- The Bile Acid Signaling Axis: Deciphering the Roles of FXR and TGR5 in Hepatic Steatosis, Fibrosis, and Cancer.Pharmacology research & perspectives · 2026Review
- Metabolic and neuroimmune control of rheumatoid arthritis: therapeutic implications of FXR and α7-nAChR axes.Inflammopharmacology · 2026Review
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Biological functions and pharmacological behaviors of bile acids in metabolic diseases.Journal of advanced research · 2025Review
- Farnesoid X Receptor Alleviates Cisplatin-Induced Kidney Inflammatory Injury by Inhibiting Tlr4/NF-κB Pathway.Journal of cellular and molecular medicine · 2025Article
- Human umbilical cord mesenchymal stem cell-derived exosomes repair IBD by activating the SIRT1-FXR pathway in macrophages.Stem cell research & therapy · 2025Article
- Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysis.Endocrine connections · 2025Article
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- OiScience · 2024Article
- Suppression of Lung Oxidative Stress, Inflammation, and Fibrosis following Nitrogen Mustard Exposure by the Selective Farnesoid X Receptor Agonist Obeticholic Acid.The Journal of pharmacology and experimental therapeutics · 2024Article
- Berberine Protects against High-Energy and Low-Protein Diet-Induced Hepatic Steatosis: Modulation of Gut Microbiota and Bile Acid Metabolism in Laying Hens.International journal of molecular sciences · 2023Article
- Heterogeneous population of macrophages in the development of non-alcoholic fatty liver disease.Liver research (Beijing, China) · 2023Review
- Macrophage metabolism in nonalcoholic fatty liver disease.Frontiers in immunology · 2023Review
- The Multifaceted Roles of Macrophages in NAFLD Pathogenesis.Cellular and molecular gastroenterology and hepatology · 2023Review
- The diverse roles of macrophages in metabolic inflammation and its resolution.Frontiers in cell and developmental biology · 2023Review
- The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity.International journal of molecular sciences · 2022Review
- Mesenchymal Stromal Cells Overexpressing Farnesoid X Receptor Exert Cardioprotective Effects Against Acute Ischemic Heart Injury by Binding Endogenous Bile Acids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Bile acids and their receptors: modulators and therapeutic targets in liver inflammation.Seminars in immunopathology · 2022Review
- Bile acids and salt-sensitive hypertension: a role of the gut-liver axis.American journal of physiology. Heart and circulatory physiology · 2022Review
- Farnesoid-X receptor as a therapeutic target for inflammatory bowel disease and colorectal cancer.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo examine the effect of farnesoid X receptor (FXR) activation by GW4064 on endotoxin-induced hepatic inflammation in nonalcoholic fatty liver disease (NAFLD) and the underlying mechanism.
methodsSix-week-old male C57BL/6 mice were fed a normal diet or a high-fat (HF) diet for 8 wk. HF diet-fed mice were intraperitoneally injected with GW4064 (30 mg/kg) or DMSO (vehicle) once daily for a week and then sacrificed after lipopolysaccharide (LPS, 50 μg/mouse) administration. Hepatic inflammation, levels of the macrophage marker F4/80, and apoptosis were measured at the end of the study. Additionally, the expression of proinflammatory genes involved in NAFLD (interleukin-6, interleukin-1β, interferon-γ, MCP-1) were analyzed by real-time PCR in the murine macrophage cell line RAW 264.7 cultured with or without GW4064 (2 μmol/L) before treatment with LPS.
resultsIn patients with NAFLD, the expression of FXR was detected by immunohistochemical staining and the relation between FXR expression and NAFLD activity score (NAS) was analyzed. Activation of FXR by GW4064 alleviated hepatic inflammation induced by endotoxin in a murine NAFLD model fed an HF diet as reflected by reduced serum levels of aspartate aminotransferase and alanine aminotransferase. Apoptosis and proinflammatory cytokine levels in liver tissues were also reduced by GW4064, and GW4064 could reduce induction of proinflammatory cytokines by LPS in vitro. FXR levels were reduced in patients with non-alcoholic steatohepatitis compared with healthy controls and were negatively correlated with NAS.
conclusionFXR activation attenuates LPS-induced hepatic inflammation in murine NAFLD by reducing expression of proinflammatory cytokines in macrophages.
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