ArticleSignal transduction and targeted therapy2024
Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor).
Article in Signal transduction and targeted therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- Ovarian tumor domain-containing protein 1 deficiency attenuates metabolic dysfunction-associated steatotic liver disease by promoting the ubiquitination of HSP90α in hepatocytes.Molecular biomedicine · 2026Article
- Unlocking the Hepatoprotective Potential of Urolithin A in High-Fat Diet-Induced MASLD: Integrated Role of Oxidative Stress, Inflammation, FXR/PPAR-α, and Fibrotic Pathway.Cell biochemistry and function · 2026Article
- Mechanism of FXR signaling: from liver inflammation to hepatocellular carcinoma.Biochemistry and biophysics reports · 2026Review
- ZBTB18 Dysfunction Promotes Neuropathic Pain via CHD4-based Epigenetic Disinhibition of CLIC1 Channels in Sensory Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RNF90 promotes hepatic steatosis by degrading CPT1α to suppress fatty acid oxidation.The Journal of biological chemistry · 2026Article
- NLR inflammasome pathways: key targets for pathogenesis and therapy of metabolic diseases.Frontiers in immunology · 2026Review
- Ubiquitin-Modifying Enzymes as Cell-Fate Regulators in Intestinal Inflammation.International journal of biological sciences · 2026Review
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- Article
- HFD Exacerbates Hepatic Lipid Metabolism Disorders After Cholecystectomy by Regulating the Bile Acid and Neutrophil Recruitment.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- From Nuclear Receptor Regulation to Spleen Activating and Accumulation Resolving Therapy: A Review of Traditional Chinese Medicine Against Diabetes and Inflammation.International journal of molecular sciences · 2025Review
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- FXR protects against neonatal sepsis by enhancing the immunosuppressive function of MDSCs.Cellular & molecular immunology · 2025Article
- FXR activation suppresses NF-κB signaling, proliferation and migration in cervical cancer cells.Translational cancer research · 2025Article
- Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5.International journal of molecular sciences · 2025Review
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- TBA-MLR score: a metabolic-immune prognostic biomarker for postoperative hepatocellular carcinoma.Frontiers in immunology · 2025Article
- Minocycline prevents early age-related cognitive decline in a mouse model of intellectual disability caused by ZBTB18/RP58 haploinsufficiency.Journal of neuroinflammation · 2024Article
- Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective.Metabolites · 2024Review
- The lack of PPARα exacerbated the progression of non-alcoholic steatohepatitis in mice with spleen deficiency syndrome by triggering an inflammatory response.Frontiers in immunology · 2024Article
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Authors and funding
21 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease (NAFLD), coupled with hepatitis and insulin resistance. Yet the details of the underlying mechanisms are not fully understood. Here, we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of NAFLD. Hepatic Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation (FAO), and induced insulin resistance. Conversely, hepatic Zbtb18 overexpression alleviated hepato-steatosis, insulin resistance, and hyperglycemia in mice fed on a high-fat diet (HFD) or in diabetic mice. Notably, in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor (FXR) mediated FAO and Clathrin Heavy Chain (CLTC) protein hinders NLRP3 inflammasome activity. This key mechanism by which hepatocyte's Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR's deletion and forced expression in mice and cultured mouse primary hepatocytes (MPHs). Moreover, CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in macrophages. Altogether, Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression, which inhibits NLRP3 inflammasome's activity alleviating inflammatory stress and insulin resistance, representing an attractive remedy for hepatic steatosis and fibrosis.
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