ArticleScientific reports2022
Exendin-4 alleviates steatosis in an in vitro cell model by lowering FABP1 and FOXA1 expression via the Wnt/-catenin signaling pathway.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- GLP-1 RAs for Treating Metabolic Dysfunction-Associated Steatosis Liver Disease: From GLP-1 Discovery to FDA Approval: A Comprehensive Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Polymer-lipid hybrid nanoparticles incorporating green coffee extract: enhancing treatment for hepatic steatosis and fibrosis through metabolomic insights.RSC advances · 2025Article
- Engineered GLP-1R-targeting nanoplatforms: multimodal therapeutics in human diseases.Journal of nanobiotechnology · 2025Review
- Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis.International journal of molecular sciences · 2025Review
- Exploring the Putative Involvement of MALAT1 in Mediating the Beneficial Effect of Exendin-4 on Oleic Acid-Induced Lipid Accumulation in HepG2 Cells.Biomedicines · 2025Article
- Macrophage-tregs crosstalk: the "hub" of the immune network in MASLD.Frontiers in immunology · 2025Review
- Exendin-4 blockade of T1R2/T1R3 activation improves Pseudomonas aeruginosa-related pneumonia in an animal model of chemically induced diabetes.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Covalent Degrader of the Oncogenic Transcription Factor β-Catenin.Journal of the American Chemical Society · 2024Article
- Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1.International journal of molecular sciences · 2024Article
- The Multifunctional Family of Mammalian Fatty Acid-Binding Proteins.Annual review of nutrition · 2023Review
- Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD.International journal of molecular sciences · 2023Review
- Iron oxide nanoparticles trigger endoplasmic reticulum damage in steatotic hepatic cells.Nanoscale advances · 2023Article
- Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells.International journal of molecular sciences · 2023Article
- [Progress on three-dimensional cell culture technology and their application].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2023Review
- Dissecting specific Wnt components governing osteogenic differentiation potential by human periodontal ligament stem cells through interleukin-6.Scientific reports · 2023Article
- The Role of GLP1-RAs in Direct Modulation of Lipid Metabolism in Hepatic Tissue as Determined Using In Vitro Models of NAFLD.Current issues in molecular biology · 2023Review
- Curcumin and Andrographolide Co-Administration Safely Prevent Steatosis Induction and ROS Production in HepG2 Cell Line.Molecules (Basel, Switzerland) · 2023Article
- Liraglutide Attenuates Hepatic Oxidative Stress, Inflammation, and Apoptosis in Streptozotocin-Induced Diabetic Mice by Modulating the Wnt/Mediators of inflammation · 2023Article
- Considering the protective effect of exendin-4 against oxidative stress in spiral ganglion neurons.Iranian journal of basic medical sciences · 2023Article
- The role of FOXA family transcription factors in glucolipid metabolism and NAFLD.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide. Agonists of the glucagon-like peptide-1 receptor (GLP-1R), currently approved to treat type 2 diabetes, hold promise to improve steatosis and even steatohepatitis. However, due to their pleiotropic effects, the mechanisms underlying their protective effect on NAFLD remain elusive. We aimed to investigate these mechanisms using an in vitro model of steatosis treated with the GLP-1R agonist Exendin-4 (Ex-4). We established steatotic HepG2 cells by incubating the cells with 400 µM oleic acid (OA) overnight. Further treatment with 200 nM Ex-4 for 3 h significantly reduced the OA-induced lipid accumulation (p < 0.05). Concomitantly, Ex-4 substantially reduced the expression levels of Fatty Acid-Binding Protein 1 (FABP1) and its primary activator, Forkhead box protein A1 (FOXA1). Interestingly, the silencing of β-catenin with siRNA abolished the effect of Ex-4 on these genes, suggesting dependency on the Wnt/β-catenin pathway. Additionally, after β-catenin silencing, OA treatment significantly increased the expression of nuclear transcription factors SREBP-1 and TCF4, whereas Ex-4 significantly decreased this upregulation. Our findings suggest that direct activation of GLP-1R by Ex-4 reduces OA-induced steatosis in HepG2 cells by reducing fatty acid uptake and transport via FABP1 downregulation.
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