ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Hepatic MDM2 Causes Metabolic Associated Fatty Liver Disease by Blocking Triglyceride-VLDL Secretion via ApoB Degradation.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- E3 Ubiquitin Ligases in MASH-Associated Liver Fibrosis: Mechanisms and Therapeutic Opportunities.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Dietary Supplementation of L-Carnosine Attenuates High Starch-Induced Disorders of Carbohydrate and Lipid Metabolisms in Zebrafish.International journal of molecular sciences · 2026Article
- Liver-specific delivery of MDM2 antisense oligonucleotides counteracts diet-induced metabolic-dysfunction-associated steatotic liver diseases.Molecular therapy. Nucleic acids · 2026Article
- Comparative analysis of renal dysfunction, immune remodeling, and gut microbiota profiles in dietary models of metabolic liver disease.BMC nephrology · 2026Article
- Environmentally relevant lanthanum chloride exposure induces hepatic steatosis in zebrafish larvae via PPARα-dependent ApoB suppression.Communications biology · 2026Article
- Article
- BLOC1S1 Attenuates B. Melitensis 16M LPS-Triggered Autophagy by Spatial Confinement of TDP-43.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulatory role of sirtuin-1 by targeting MDM2 to mitochondria-associated membranes formation in the treatment of NAFLD.Cell communication and signaling : CCS · 2025Article
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Exomeres and supermeres: Current advances and perspectives.Bioactive materials · 2025Review
- Metabolic Dysfunction-Associated Steatotic Liver Disease: From a Very Low-Density Lipoprotein Perspective.Biomolecules · 2025Review
- Unveiling lipoprotein subfractions signature in high-FNPO PCOS: implications for PCOM diagnosis and risk assessment using advanced machine learning models.BMC medicine · 2025Article
- Walking the VLDL tightrope in cardiometabolic diseases.Trends in endocrinology and metabolism: TEM · 2025Review
- Association of Life's Essential 8 and Life's Simple 7 with metabolic-associated fatty liver disease in the United States.World journal of hepatology · 2025Article
- Prevalence and risk factors of metabolic associated fatty liver disease in lean patients with bipolar disorder: a retrospective cross-sectional study.Frontiers in endocrinology · 2025Article
- Molecular Regulation and Therapeutic Targeting of VLDL Production in Cardiometabolic Disease.Cellular and molecular gastroenterology and hepatology · 2025Review
- Nuclear Receptor-Targeted Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of drug discovery and pharmacology · 2025Article
- GCKIII kinases control hepatocellular lipid homeostasis via shared mode of action.Journal of lipid research · 2024Article
- MDM2 induces pro-inflammatory and glycolytic responses in M1 macrophages by integrating iNOS-nitric oxide and HIF-1α pathways in mice.Nature communications · 2024Article
- MAFLD as part of systemic metabolic dysregulation.Hepatology international · 2024Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 4 countries.
Funding
Abstract
Dysfunctional triglyceride-very low-density lipoprotein (TG-VLDL) metabolism is linked to metabolic-associated fatty liver disease (MAFLD); however, the underlying cause remains unclear. The study shows that hepatic E3 ubiquitin ligase murine double minute 2 (MDM2) controls MAFLD by blocking TG-VLDL secretion. A remarkable upregulation of MDM2 is observed in the livers of human and mouse models with different levels of severity of MAFLD. Hepatocyte-specific deletion of MDM2 protects against high-fat high-cholesterol diet-induced hepatic steatosis and inflammation, accompanied by a significant elevation in TG-VLDL secretion. As an E3 ubiquitin ligase, MDM2 targets apolipoprotein B (ApoB) for proteasomal degradation through direct protein-protein interaction, which leads to reduced TG-VLDL secretion in hepatocytes. Pharmacological blockage of the MDM2-ApoB interaction alleviates dietary-induced hepatic steatohepatitis and fibrosis by inducing hepatic ApoB expression and subsequent TG-VLDL secretion. The effect of MDM2 on VLDL metabolism is p53-independent. Collectively, these findings suggest that MDM2 acts as a negative regulator of hepatic ApoB levels and TG-VLDL secretion in MAFLD. Inhibition of the MDM2-ApoB interaction may represent a potential therapeutic approach for MAFLD 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 Socratic graph.