ArticleNature communications2016
Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 121 citations in OpenAlex.
- Clinical applications and challenges of CD40/CD40L signaling regulation in autoimmune diseases.Frontiers in immunology · 2026Review
- Article
- Aberrant alternative splicing in alcoholic hepatitis: regulatory roles of RBPs and sQTLs.BMC gastroenterology · 2025Article
- Influenza virus infection reprograms cholesterol biosynthesis to facilitate virus replication by the TAK1-RORγ axis.PLoS pathogens · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Nano-Selenium Modulates NF-κB/NLRP3 Pathway and Mitochondrial Dynamics to Attenuate Microplastic-Induced Liver Injury.Nutrients · 2024Article
- Cardiomyocyte-specific knockout of ADAM17 alleviates doxorubicin-induced cardiomyopathy via inhibiting TNFα-TRAF3-TAK1-MAPK axis.Signal transduction and targeted therapy · 2024Article
- USP13 ameliorates nonalcoholic fatty liver disease through inhibiting the activation of TAK1.Journal of translational medicine · 2024Article
- Tumor necrosis factor receptor-associated factor 5 protects against intimal hyperplasia by regulation of macrophage polarization via directly targeting PPARγ.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Functional Food Chemical Ingredient Strategies for Non-alcoholic Fatty Liver Disease (NAFLD) and Hepatic Fibrosis: Chemical Properties, Health Benefits, Action, and Application.Current nutrition reports · 2024Review
- Hepatocyte programmed cell death: the trigger for inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis.Frontiers in cell and developmental biology · 2024Review
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Zinc finger transcription factor Egf1 promotes non-alcoholic fatty liver disease.JHEP reports : innovation in hepatology · 2023Article
- Adipose-specific deletion of the cation channel TRPM7 inhibits TAK1 kinase-dependent inflammation and obesity in male mice.Nature communications · 2023Article
- Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease.Biomedicines · 2022Review
- Progress and Prospects of Non-Canonical NF-κB Signaling Pathway in the Regulation of Liver Diseases.Molecules (Basel, Switzerland) · 2022Review
- Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis.Cell death discovery · 2022Article
- The E3 ubiquitin-protein ligase Trim31 alleviates non-alcoholic fatty liver disease by targeting Rhbdf2 in mouse hepatocytes.Nature communications · 2022Article
- Deletion of RNF186 expression suppresses diet-induced hepatic steatosis by regulating insulin activity.iScience · 2022Article
- Systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE-Knockout mice.FASEB bioAdvances · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and a systemic pro-inflammatory response. Here we show that tumour necrosis factor receptor-associated factor 3 (TRAF3) is upregulated in mouse and human livers with hepatic steatosis. After 24 weeks on a high-fat diet (HFD), obesity, insulin resistance, hepatic steatosis and inflammatory responses are significantly ameliorated in liver-specific TRAF3-knockout mice, but exacerbated in transgenic mice overexpressing TRAF3 in hepatocytes. The detrimental effects of TRAF3 on hepatic steatosis and related pathologies are confirmed in ob/ob mice. We further show that in response to HFD, hepatocyte TRAF3 binds to TGF-β-activated kinase 1 (TAK1) to induce TAK1 ubiquitination and subsequent autophosphorylation, thereby enhancing the activation of downstream IKKβ-NF-κB and MKK-JNK-IRS1(307) signalling cascades, while disrupting AKT-GSK3β/FOXO1 signalling. The TRAF3-TAK1 interaction and TAK1 ubiquitination are indispensable for TRAF3-regulated hepatic steatosis. In conclusion, hepatocyte TRAF3 promotes HFD-induced or genetic hepatic steatosis in a TAK1-dependent manner.
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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.