ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2023
Involvement of eNAMPT/TLR4 inflammatory signaling in progression of non-alcoholic fatty liver disease, steatohepatitis, and fibrosis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 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
- Article
- Visnagin Attenuates Thioacetamide-Induced Liver Injury and Fibrosis Through the Modulation of TLR4-Mediated Inflammation and Downregulation of TGF-β/α-SMA-Driven Fibrogenesis.Journal of applied toxicology : JAT · 2026Article
- Spatial analysis reveals cellular microenvironments and mechanisms of inflammation and injury in acute interstitial nephritis.Nature communications · 2026Article
- Hidradenitis suppurativa: epidemiology, diagnosis, molecular pathogenesis and therapy.Molecular biomedicine · 2026Review
- Adipose-Derived Proinflammatory Visfatin Promotes Vascular Calcification via TLR4 and is Suppressed by Empagliflozin.Inflammation · 2026Article
- NAMPT improves high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) via the SIRT1-C/EBPβ-STEAP4-NRF2 axis.Journal of molecular cell biology · 2026Article
- TLR4-Mediated Immune Dysfunction Links MASLD and Parkinson's Disease: Insights from an Omics-Based Network Analysis.NeuroSci · 2026Article
- Circulating eNAMPT in Glaucoma: A Semi-Quantitative Plasma Analysis Before and After Nicotinamide Supplementation.Translational vision science & technology · 2026Article
- Inhibiting Nampt signaling promotes M2 macrophage polarization to enhance bone regeneration in periodontitis.Frontiers in bioengineering and biotechnology · 2026Article
- NAMPT orchestrates fibroblast cuproptosis and immune crosstalk during IPF progression.Frontiers in immunology · 2026Article
- eNAMPT/TLR4 signaling drives PAH cellular phenotypic switching and lung vascular remodeling.Cell communication and signaling : CCS · 2025Article
- eNAMPT Is a Novel DAMP and Therapeutic Target in Human and Murine Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2025Article
- Nicotinamide phosphoribosyltransferase in NADCell death discovery · 2025Review
- NEDD4 E3 ligase-catalyzed NAMPT ubiquitination and autophagy activation are essential for pyroptosis-independent NAMPT secretion in human monocytes.Cell communication and signaling : CCS · 2025Article
- Chemokines as potential biomarkers for predicting the course of COVID-19 - a review of the literature.Frontiers in immunology · 2025Review
- Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives.ADMET & DMPK · 2025Review
- Allelic, Genotypic, and Haplotypic Analysis of Cytokine IL17A, IL17F, and Toll-like Receptor TLR4 Gene Polymorphisms in Metabolic-Dysfunction-Associated Steatotic Liver Disease: Insights from an Exploratory Study.Life (Basel, Switzerland) · 2024Article
- Genetic and epigenetic regulation of cortactin (CTTN) by inflammatory factors and mechanical stress in human lung endothelial cells.Bioscience reports · 2024Article
- Safety, Tolerability and Pharmacokinetics of the eNAMPT-Neutralizing ALT-100 Mab in Healthy Volunteers.Journal of clinical research and clinical trials · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Although the progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to steatohepatitis (NASH) and cirrhosis remains poorly understood, a critical role for dysregulated innate immunity has emerged. We examined the utility of ALT-100, a monoclonal antibody (mAb), in reducing NAFLD severity and progression to NASH/hepatic fibrosis. ALT-100 neutralizes eNAMPT (extracellular nicotinamide phosphoribosyltransferase), a novel damage-associated molecular pattern protein (DAMP) and Toll-like receptor 4 (TLR4) ligand. Histologic and biochemical markers were measured in liver tissues and plasma from human NAFLD subjects and NAFLD mice (streptozotocin/high-fat diet-STZ/HFD, 12 weeks). Human NAFLD subjects (n = 5) exhibited significantly increased NAMPT hepatic expression and significantly elevated plasma levels of eNAMPT, IL-6, Ang-2, and IL-1RA compared to healthy controls, with IL-6 and Ang-2 levels significantly increased in NASH non-survivors. Untreated STZ/HFD-exposed mice displayed significant increases in NAFLD activity scores, liver triglycerides, NAMPT hepatic expression, plasma cytokine levels (eNAMPT, IL-6, and TNFα), and histologic evidence of hepatocyte ballooning and hepatic fibrosis. Mice receiving the eNAMPT-neutralizing ALT-100 mAb (0.4 mg/kg/week, IP, weeks 9 to 12) exhibited marked attenuation of each index of NASH progression/severity. Thus, activation of the eNAMPT/TLR4 inflammatory pathway contributes to NAFLD severity and NASH/hepatic fibrosis. ALT-100 is potentially an effective therapeutic approach to address this unmet NAFLD need.
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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.