ArticleGut2007
Free fatty acids sensitise hepatocytes to TRAIL mediated cytotoxicity.
Article in Gut, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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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.
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Who cites it
115 citing papers in PubMed, 212 citations in OpenAlex.
- A phase 2, randomized, double-blind, placebo-controlled study of GS-9450 in subjects with nonalcoholic steatohepatitis.Hepatology (Baltimore, Md.) · 2012Trial
- Six-compound cocktail for maturation of human pluripotent stem cell-derived liver spheroids for toxicity prediction.Nature communications · 2026Article
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- The Intriguing Roles of Cytokines in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review.Current obesity reports · 2025Review
- Targeting cell death in NAFLD: mechanisms and targeted therapies.Cell death discovery · 2024Review
- Lipotoxicity, ER Stress, and Cardiovascular Disease: Current Understanding and Future Directions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Nonalcoholic Fatty Liver Disease and Staging of Hepatic Fibrosis.Advances in experimental medicine and biology · 2024Review
- Mechanisms of liver fibrosis in metabolic syndrome.eGastroenterology · 2023Article
- Plasma-Derived Exosomes from NAFLD Patients Modulate the Cannabinoid Receptors' Expression in Cultured HepaRG Cells.International journal of molecular sciences · 2023Article
- Protective Effect of Vitamin D against Hepatic Molecular Apoptosis Caused by a High-Fat Diet in Rats.Current issues in molecular biology · 2023Article
- Indirubin Inhibits TRAIL-Induced Activation of Death Receptor 5 in Jurkat Cells.Natural product communications · 2023Article
- Review
- Stress kinases in the development of liver steatosis and hepatocellular carcinoma.Molecular metabolism · 2021Review
- Transformation of SOX9Scientific reports · 2021Article
- Pathophysiological Aspects of Alcohol Metabolism in the Liver.International journal of molecular sciences · 2021Review
- Comparison of Chemical Composition and Biological Activities of EightPharmaceuticals (Basel, Switzerland) · 2020Article
- Autophagy alleviates amiodarone-induced hepatotoxicity.Archives of toxicology · 2020Article
- Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?Cell death & disease · 2020Review
- Extracellular Vesicles as Inflammatory Drivers in NAFLD.Frontiers in immunology · 2020Review
- Non-alcoholic Fatty Liver Disease and Alcohol-Related Liver Disease: Two Intertwined Entities.Frontiers in medicine · 2020Review
55 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
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundElevated circulating free fatty acids (FFA) contribute to the development of hepatic steatosis and promote hepatocyte apoptosis by incompletely defined mechanisms. Although the death ligand TRAIL has been implicated in a variety of pathological liver diseases, the role of TRAIL in mediating apoptosis of FFA induced steatotic hepatocytes is unknown.
aimWe examined TRAIL cytotoxicity in an in vitro model of hepatocyte steatosis induced by FFA.
methodsHepatocytes (Huh 7 cells, HepG2 cells, and primary rat hepatocytes) were rendered steatotic by incubation with oleic acid. Apoptosis was assessed morphologically and biochemically by caspase activity. TRAIL receptor regulation was examined using immunoblot analysis and siRNA for targeted knockdown. c-jun N-terminal kinase (JNK) inhibition was attained with SP600125.
resultsOleic acid sensitised the cells to TRAIL but not TNF-alpha cytotoxicity. FFA sensitisation to TRAIL occurred at much lower concentrations than required for FFA mediated sensitisation to Fas, or FFA induced lipoapoptosis. Oleic acid treatment led to upregulation of the cognate TRAIL receptor death receptor 5 (DR5) but not death receptor 4 (DR4). The upregulation of DR5 was JNK dependent. siRNA targeted knockdown of either DR5 or DR4 demonstrated that DR5 was responsible for FFA sensitisation to TRAIL killing. DR5 expression was enhanced in steatotic human liver samples.
conclusionOur results suggest that FFA induced hepatocyte steatosis sensitises to TRAIL by a DR5 mediated JNK dependent mechanism.
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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.