ArticleAntioxidants & redox signaling2015
Reactive oxygen species-induced TXNIP drives fructose-mediated hepatic inflammation and lipid accumulation through NLRP3 inflammasome activation.
Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.
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Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 231 citations in OpenAlex.
- Multi-target synergistic mechanisms of flavonoid compounds from traditional Chinese medicine in non-alcoholic fatty liver disease: insights for human and veterinary medicine.Frontiers in veterinary science · 2026Pooled it
- Dexpanthenol Attenuates High-Fructose Corn Syrup-Induced Hepatic Injury in Young Adult Rats by Modulating Oxidative Stress, Apoptosis, and Inflammasome-Associated Pyroptotic Signaling.International journal of molecular sciences · 2026Article
- TCM-Guided Targeted Therapies Against NLRP3 Inflammasome in NAFLD.Immunity, inflammation and disease · 2026Review
- Long-Term Static Cultivation Alters Lipid Metabolism and Bioenergetic Capacity in A549 Cells.International journal of molecular sciences · 2026Article
- Alogliptin repositioning confers protection against diclofenac-induced liver injury by inhibiting TLR4/NF-κB, ROS/TXNIP, and NLRP3 inflammasome-mediated pyroptosis in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- Neuroprotective effects of ROCK inhibition on hippocampal energy metabolism in a rat model of metabolic syndrome.Iranian journal of basic medical sciences · 2026Article
- When glycobiology meets inflammasome activation: Insights and implications.Journal of advanced research · 2026Review
- Metaflammation's Role in Systemic Dysfunction in Obesity: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Benzo[a]pyrene aggravated ovalbumin‑induced epithelial tight junction disruption via ROS driven‑NLRP3/Caspase‑1 signaling pathway in asthmatic mice.International journal of molecular medicine · 2025Article
- Fructose metabolism and its roles in metabolic diseases, inflammatory diseases, and cancer.Molecular biomedicine · 2025Review
- Mechanism of action of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome and its regulation in liver injury.Chinese medical journal · 2025Review
- Genome editing of TXNIP in human pluripotent stem cells for the generation of hepatocyte-like cells and insulin-producing islet-like aggregates.Stem cell research & therapy · 2025Article
- Molecular Mechanism of Aerobic Exercise Ameliorating Myocardial Mitochondrial Injury in Mice with Heart Failure.International journal of molecular sciences · 2025Article
- pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation.Cell death discovery · 2025Article
- Research progress on quercetin in improving the survival rate of random skin flap.Archives of dermatological research · 2025Review
- Article
- Epigallocatechin-3-Gallate Ameliorates Diabetic Kidney Disease by Inhibiting the TXNIP/NLRP3/IL-1β Signaling Pathway.Food science & nutrition · 2024Article
- The role of quercetin in NLRP3-associated inflammation.Inflammopharmacology · 2024Review
- Celastrol ameliorates hypoxic-ischemic brain injury in neonatal rats by reducing oxidative stress and inflammation.Pediatric research · 2024Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsIncreased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation.
resultsRats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. INNOVATION AND
conclusionsThis study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant-based interventions can inhibit the ROS-TXNIP pathway.
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