ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Hepatic TLR4 signaling in obese NAFLD.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 237 citations in OpenAlex.
- Gut microbiota shaping fatty liver disease progression.Life science alliance · 2027Review
- Gut microbes mediate the synergistic effects of dietary cholesterol and saturated fat in driving fibrosing MASH.Gut microbes · 2026Article
- Fatty acid species differentially regulate macrophage polarization and oxidative stress with secondary effects on macrophage-HSC crosstalk.Physiological reports · 2026Article
- Chronic infection and metabolic stress: a converging axis driving hypertension and metabolic dysfunction-associated steatotic liver disease outcomes.American journal of hypertension · 2026Review
- Breast Cancer and Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- Gut Microbiota, Diet and Lipid Metabolism in Adolescents with NAFLD and Their Role in Preventive Strategies.International journal of molecular sciences · 2026Review
- TLR4-Mediated Immune Dysfunction Links MASLD and Parkinson's Disease: Insights from an Omics-Based Network Analysis.NeuroSci · 2026Article
- Superior inflammatory response and MASH progression inFrontiers in immunology · 2026Article
- Metabolic dysfunction‑associated steatotic liver disease: Pathogenesis, model and treatment (Review).International journal of molecular medicine · 2025Review
- The Vicious Circle of Metabolic Dysfunction-Associated Steatotic Liver Disease When Micronutrient Deficiency Drives Microbial Imbalance and Liver Injury.Life (Basel, Switzerland) · 2025Review
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
- Paired snRNA-seq and scRNA-seq analysis of MASLD patients to identify early-stage markers for disease progression.Hepatology communications · 2025Article
- Postprandial Metabolism, Inflammation, and Plasma Bile Acid Kinetics in a Rat Model: Implications for Translational Research.Molecular nutrition & food research · 2025Article
- Ambroxol mitigates cyclophosphamide-induced liver injury by suppressing TLR-4/NF-κB signaling and oxidative stress and upregulating cytoglobin, TXNRD1 and HMGB1.World journal of gastroenterology · 2025Article
- Microbiota-driven epigenetic modifications in gastrointestinal cancer: Implications for pathogenesis and therapeutic strategies.World journal of microbiology & biotechnology · 2025Review
- Gut microbiota in non-alcoholic fatty liver disease: Pathophysiology, diagnosis, and therapeutics.World journal of hepatology · 2025Review
- Effect of Supplementation of Antioxidant Lipids Synthetized by Enzymatic Acidolysis with EPA/DHA Concentrate and Maqui (Antioxidants (Basel, Switzerland) · 2025Article
- Phytochemicals Targeting Inflammatory Pathways in Alcohol-Induced Liver Disease: A Mechanistic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Metabolic dysfunction-associated steatotic liver disease and the gut microbiome: pathogenic insights and therapeutic innovations.The Journal of clinical investigation · 2025Review
- Therapeutic potential of elafibranor in alcohol-associated liver disease: Insights into macrophage modulation and fibrosis reduction.World journal of biological chemistry · 2025Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease occurs frequently in the setting of metabolic syndrome, but the factors leading to nonalcoholic steatohepatitis (NASH) are not fully understood. This study investigated Toll-like receptor 4 (TLR4) signaling in human liver with the goal of delineating whether activation of this pathway segregates those with nonalcoholic fatty liver from those with NASH. Experiments were performed using liver biopsy tissue obtained from class III obese subjects undergoing bariatric surgery, and extended to an immortalized human hepatocyte HepaRG cell line and primary human hepatocytes. The bacterial endotoxin lipopolysaccharide (LPS) and total free fatty acid levels were significantly increased in plasma of NASH patients. TLR4 mRNA levels were significantly increased in subjects with NASH compared with NAFL as was interferon regulatory factor (IRF) 3 in the myeloid differentiation factor 88-independent signaling pathway. In HepaRG cells, nuclear factor-κB (NF-κB) nuclear translocation and functional activity increased following treatment with the fatty acid, palmitate, and following exposure to LPS compared with hepatocytes stimulated with a lipogenic treatment that induced de novo lipogenesis. Palmitate and LPS induction of NF-κB activity was partially attenuated by chemical- or small-interfering RNA-mediated inhibition of TLR4. Expression of TLR4 and its downstream mediators was upregulated with palmitate and LPS. Similar results were observed using primary human hepatocytes from a lean donor. Interestingly, NF-κB activity assays showed obese donor hepatocytes were resistant to chemical TLR4 inhibition. In conclusion, TLR4 expression is upregulated in a large cohort of NASH patients, compared with those with NAFL, and this occurs within the setting of increased LPS and fatty acids.
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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.