ArticleScientific reports2018
The PPARα Agonist Fenofibrate Prevents Formation of Protein Aggregates (Mallory-Denk bodies) in a Murine Model of Steatohepatitis-like Hepatotoxicity.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications.MedComm · 2025Review
- Pemafibrate Reduced Liver Stiffness in Patients with Metabolic Dysfunction-associated Steatotic Liver Disease Complicated with Hyperlipidemia and Liver Fibrosis with a Fibrosis-4 Index Above 1.3.Internal medicine (Tokyo, Japan) · 2025Article
- Therapeutic potential of elafibranor in alcohol-associated liver disease: Insights into macrophage modulation and fibrosis reduction.World journal of biological chemistry · 2025Review
- Anti-inflammatory role of fenofibrate in treating diseases.Biomolecules & biomedicine · 2023Review
- Plasma Cytokeratin-18 Fragment Level Reflects the Metabolic Phenotype in Obesity.Biomolecules · 2023Article
- PPARα in the Epigenetic Driver Seat of NAFLD: New Therapeutic Opportunities for Epigenetic Drugs?Biomedicines · 2022Review
- PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients.International journal of molecular sciences · 2022Review
- Liver Protective Effect of Fenofibrate in NASH/NAFLD Animal Models.PPAR research · 2022Review
- Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis.International journal of molecular sciences · 2021Article
- Different Roles of p62 (SQSTM1) Isoforms in Keratin-Related Protein Aggregation.International journal of molecular sciences · 2021Article
- Review
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Chronic intoxication of mice with the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) leads to morphological and metabolic changes closely resembling steatohepatitis, a severe form of metabolic liver disease in humans. Since human steatohepatitis (both the alcoholic and non-alcoholic type) is characterized by reduced expression of PPARα and disturbed lipid metabolism we investigated the role of this ligand-activated receptor in the development of DDC-induced liver injury. Acute DDC-intoxication was accompanied by early significant downregulation of Pparα mRNA expression along with PPARα-controlled stress-response and lipid metabolism genes that persisted in the chronic stage. Administration of the specific PPARα agonist fenofibrate together with DDC prevented the downregulation of PPARα-associated genes and also improved the stress response of Nrf2-dependent redox-regulating genes. Moreover, oxidative stress and inflammation were strongly reduced by DDC/fenofibrate co-treatment. In addition, fenofibrate prevented the disruption of hepatocyte intermediate filament cytoskeleton and the formation of Mallory-Denk bodies at late stages of DDC intoxication. Our findings show that, like in human steatohepatitis, PPARα is downregulated in the DDC model of steatohepatitis-like hepatocellular damage. Its downregulation and the pathomorphologic features of steatohepatitis are prevented by co-administration of fenofibrate.
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