ArticleCell death and differentiation2024
Ferroptosis is a targetable detrimental factor in metabolic dysfunction-associated steatotic liver disease.
Article in Cell death and differentiation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Bibliometric analysis and visualization of ferroptosis in metabolic dysfunction-associated steatotic liver disease (MASLD): a comprehensive review.Frontiers in pharmacology · 2026Pooled it
- Metabolic dysfunction-associated steatotic liver disease: pathogenic mechanisms and exercise-induced molecular adaptations.Lipids in health and disease · 2026Review
- The Spatial Redox-Metalloptosis Axis in Liver Disease: A Hypothesis on Regional Susceptibility to Ferroptosis and Cuproptosis.Antioxidants (Basel, Switzerland) · 2026Review
- The Latest Therapeutic Targets and New Drug Research of Metabolic Dysfunction-Associated Steatotic Liver Disease.Clinical pharmacology and therapeutics · 2026Review
- Gut-Liver Translocation of Bacteroides Uniformis Alleviates Advanced Metabolic Dysfunction-Associated Steatotic Liver Disease by Suppressing Hepatocyte Ferroptosis via Propionic Acid Secretion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hepatocyte hedgehog signaling controls ferroptosis to alleviate aging-related organ dysfunction.JCI insight · 2026Article
- Review
- A new lens on ferroptosis in liver disease: Near-infrared fluorescent probe of lipid peroxidation-driven microenvironmental remodeling: Editorial on "Novel near-infrared probe for monitoring lipid peroxidation-mediated viscosity change in ferroptotic hepatocytes".Clinical and molecular hepatology · 2026Article
- DN203316, a novel PPARδ agonist, suppresses ferroptotic signaling and fibrogenesis in metabolic dysfunction-associated steatohepatitis.Experimental & molecular medicine · 2026Article
- Modulation of Ferroptosis During EarlybioRxiv : the preprint server for biology · 2026Article
- Mendelian Randomization Analysis of Systemic Iron Status and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease.Metabolites · 2026Article
- OSBPL2 deficiency alleviates diet-induced MASLD by reducing ACSL4-mediated ferroptosis.iScience · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Metabolic dysfunction-associated steatotic liver disease: On track to become the dominant etiology of hepatocellular carcinoma: Reply to correspondence on "Downregulation of the MARC1 p.A165 risk allele reduces hepatocyte lipid content by increasing beta-oxidation".Clinical and molecular hepatology · 2026Article
- Pesticides Drive Liver Diseases Through Non-Apoptotic Regulated Cell Death Pathways.Diseases (Basel, Switzerland) · 2026Review
- Identification of 4,5,6,7-Tetrabromo-1bioRxiv : the preprint server for biology · 2026Article
- A Global Perspective on Metabolic Dysfunction-Associated Steatotic Liver Disease: From Molecular Mechanisms to Therapeutic Strategy Innovation.Nutrients · 2026Review
- Obesity impairs spermatogenesis via Leydig cell ferroptosis induced by liver-derived exosomal miR-122-5p.Communications biology · 2026Article
- Ferroptosis in metabolic dysfunction-associated steatotic liver disease.Frontiers in immunology · 2026Review
- Novel near-infrared probe for monitoring lipid peroxidation-mediated viscosity change in ferroptotic hepatocytes.Clinical and molecular hepatology · 2026Article
Corrections and comments
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Authors and funding
31 authors.
Funding
Abstract
There is an unmet clinical need for pharmacologic treatment for metabolic dysfunction-associated steatotic liver disease (MASLD). Hepatocyte cell death is a hallmark of this highly prevalent chronic liver disease, but the dominant type of cell death remains uncertain. Here we report that ferroptosis, an iron-catalyzed mode of regulated cell death, contributes to MASLD. Unsupervised clustering in a cohort of biopsy-proven MASLD patients revealed a subgroup with hepatic ferroptosis signature and lower glutathione peroxidase 4 (GPX4) levels. Likewise, a subgroup with reduced ferroptosis defenses was discerned in public transcriptomics datasets. Four weeks of choline-deficient L-amino acid-defined high-fat diet (CDAHFD) induced MASLD with ferroptosis in mice. Gpx4 overexpression did not affect steatohepatitis, instead CDAHFD protected from morbidity due to hepatocyte-specific Gpx4 knockout. The ferroptosis inhibitor UAMC-3203 attenuated steatosis and alanine aminotransferase in CDAHFD and a second model, i.e., the high-fat high-fructose diet (HFHFD). The effect of monounsaturated and saturated fatty acids supplementation on ferroptosis susceptibility was assessed in human HepG2 cells. Fat-laden HepG2 showed a drop in ferroptosis defenses, increased phosphatidylglycerol with two polyunsaturated fatty acid (PUFA) lipid tails, and sustained ferroptosis sensitivity. In conclusion, this study identified hepatic ferroptosis as a detrimental factor in MASLD patients. Unexpectedly, non-PUFA supplementation to hepatocytes altered lipid bilayer composition to maintain ferroptosis sensitivity. Based on findings in in vivo models, ferroptosis inhibition represents a promising therapeutic target in MASLD.
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