ArticleCell death & disease2020
TNF-Receptor-1 inhibition reduces liver steatosis, hepatocellular injury and fibrosis in NAFLD mice.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.
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Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- MicroRNAs as the promising markers of comorbidities in childhood obesity-A systematic review.Pediatric obesity · 2022Pooled it
- The Roles of TNF Signaling Pathways in Metabolism of Bone Tumors.Frontiers in pharmacology · 2022Pooled it
- Effects of TNF-α in Human Precision-Cut Liver Slices and its Implications for Metabolic Dysfunction-Associated Steatohepatitis Progression.Inflammation · 2026Article
- The NF-κB Signalling Pathway: Mechanisms, Consequences and Therapeutic Targets.Journal of cellular and molecular medicine · 2026Review
- Epigenetically controlled endothelial promyelocytic leukemia drives liver inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- Innovative analysis and future prospects of Bupleuri Radix's pharmacology and toxicity based on the gut-liver axis.MedScience · 2026Review
- [SingleZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- Targeting DNA fragment extrusion: a new therapeutic avenue for CClMolecular biology reports · 2026Article
- PGC-1α protects against MASH via Tim23-dependent inhibition of DRP1-mediated ferroptosis.Cell death & disease · 2026Article
- Adenosine metabolic clearance maintains liver homeostasis by licensing arginine methylation of RIPK1.The Journal of experimental medicine · 2026Article
- Meta-inflammation in Hidradenitis suppurativa: from pathogenic evidence to therapeutic approaches.Frontiers in immunology · 2026Review
- Targeting necroptosis: how does exercise protect against metabolic dysfunction-associated fatty liver disease?Frontiers in physiology · 2026Review
- TNF as a mediator of metabolic inflammation and body-brain interaction in obesity-driven neuroinflammation and neurodegeneration.Ageing research reviews · 2025Review
- Hepatic CB1 receptor signaling triggers GMetabolism: clinical and experimental · 2025Article
- The Intriguing Roles of Cytokines in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review.Current obesity reports · 2025Review
- Three-year outcomes of tumor necrosis factor alpha inhibitor therapy in rheumatoid arthritis patients with elevated liver enzymes.World journal of hepatology · 2025Article
- Lipid Accumulation and Insulin Resistance: Bridging Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Kidney Disease.International journal of molecular sciences · 2025Review
- MASH as an emerging cause of hepatocellular carcinoma: current knowledge and future perspectives.Molecular oncology · 2025Review
- Identification of biomarkers associated with coronary artery disease and non-alcoholic fatty liver disease by bioinformatics analysis and machine learning.Scientific reports · 2025Article
- Exploring TNFR1: from discovery to targeted therapy development.Journal of translational medicine · 2025Review
29 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
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) shows an increasing prevalence and is associated with the development of liver fibrosis and cirrhosis as the major risk factors of liver-related mortality in this disease. The therapeutic possibilities are limited and restricted to life style intervention, since specific drugs for NAFLD are unavailable so far. TNFα has been implicated as a major pathogenic driver of NAFLD. TNFα-mediated liver injury occurs mainly via TNF-receptor-1 (TNFR1) signaling, whereas TNFR2 mediates protective pathways. In this study, we analyzed the therapeutic effects of a novel antibody, which selectively inhibits TNFR1 while retaining protective TNFR2 signaling in a high-fat diet (HFD) mouse model of NAFLD. Mice were fed with HFD for 32 weeks and treated with anti-TNFR1-antibody or control-antibody for the last 8 weeks. We then investigated the mechanisms of TNFR1 inhibition on liver steatosis, inflammatory liver injury, insulin resistance and fibrosis. Compared to control-antibody treatment, TNFR1 inhibition significantly reduced liver steatosis and triglyceride content, which was accompanied by reduced expression and activation of the transcription factor SREBP1 and downstream target genes of lipogenesis. Furthermore, inhibition of TNFR1 resulted in reduced activation of the MAP kinase MKK7 and its downstream target JNK, which was associated with significant improvement of insulin resistance. Apoptotic liver injury, NAFLD activity and alanine aminotransferase (ALT) levels, as well as liver fibrosis significantly decreased by anti-TNFR1 compared to control-antibody treatment. Thus, our results suggest selective TNFR1 inhibition as a promising approach for NAFLD treatment.
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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.