ArticlePloS one2015
Eicosapentaenoic acid ameliorates non-alcoholic steatohepatitis in a novel mouse model using melanocortin 4 receptor-deficient mice.
Article in PloS one, 2015. 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, 43 citations in OpenAlex.
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Disease-derived liver organoids as a preclinical screening platform identify Sargassum japonica as an anti-fibrotic candidate.Scientific reports · 2026Article
- The Microbiota and Evolution of Obesity.Endocrine reviews · 2025Review
- NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.International journal of biological sciences · 2024Article
- Dynamics of Liver Macrophage Subsets in a Novel Mouse Model of Non-Alcoholic Steatohepatitis Using C57BL/6 Mice.Biomedicines · 2023Article
- Roles of Macrophages in Advanced Liver Fibrosis, Identified Using a Newly Established Mouse Model of Diet-Induced Non-Alcoholic Steatohepatitis.International journal of molecular sciences · 2022Article
- In Vivo and In Silico Investigation of the Anti-Obesity Effects ofInternational journal of molecular sciences · 2022Article
- Lipid alterations in chronic liver disease and liver cancer.JHEP reports : innovation in hepatology · 2022Review
- Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates.Biomedicines · 2022Review
- The Effects of Probiotics and Omega-3 Fatty Acids in Liver Steatosis Induced in Rats by High-Fructose Corn Syrup.International journal of clinical practice · 2022Article
- Latency-associated Peptide Degradation Fragments Produced in Stellate Cells and Phagocytosed by Macrophages in Bile Duct-ligated Mouse Liver.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Article
- [Therapeutic mechanism of the Mongolian medicineNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Article
- Upregulation of cancer-associated gene expression in activated fibroblasts in a mouse model of non-alcoholic steatohepatitis.Scientific reports · 2019Article
- Obeticholic acid protects against hepatocyte death and liver fibrosis in a murine model of nonalcoholic steatohepatitis.Scientific reports · 2018Article
- Mouse models for investigating the underlying mechanisms of nonalcoholic steatohepatitis-derived hepatocellular carcinoma.World journal of gastroenterology · 2018Review
- Molecular mechanism of obesity-induced 'metabolic' tissue remodeling.Journal of diabetes investigation · 2018Review
- Eicosapentaenoic acid attenuates obesity-related hepatocellular carcinogenesis.Carcinogenesis · 2018Article
- Aggressive Crosstalk Between Fatty Acids and Inflammation in Macrophages and Their Influence on Metabolic Homeostasis.Neurochemical research · 2018Review
- Omega-3 polyunsaturated fatty acids as a treatment strategy for nonalcoholic fatty liver disease.Pharmacology & therapeutics · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many attempts have been made to find novel therapeutic strategies for non-alcoholic steatohepatitis (NASH), while their clinical efficacy is unclear. We have recently reported a novel rodent model of NASH using melanocortin 4 receptor-deficient (MC4R-KO) mice, which exhibit the sequence of events that comprise hepatic steatosis, liver fibrosis, and hepatocellular carcinoma with obesity-related phenotypes. In the liver of MC4R-KO mice, there is a unique histological feature termed hepatic crown-like structures (hCLS), where macrophages interact with dead hepatocytes and fibrogenic cells, thereby accelerating inflammation and fibrosis. In this study, we employed MC4R-KO mice to examine the effect of highly purified eicosapentaenoic acid (EPA), a clinically available n-3 polyunsaturated fatty acid, on the development of NASH. EPA treatment markedly prevented the development of hepatocyte injury, hCLS formation and liver fibrosis along with lipid accumulation. EPA treatment was also effective even after MC4R-KO mice developed NASH. Intriguingly, improvement of liver fibrosis was accompanied by the reduction of hCLS formation and plasma kallikrein-mediated transforming growth factor-β activation. Moreover, EPA treatment increased the otherwise reduced serum concentrations of adiponectin, an adipocytokine with anti-inflammatory and anti-fibrotic properties. Collectively, EPA treatment effectively prevents the development and progression of NASH in MC4R-KO mice along with amelioration of hepatic steatosis. This study unravels a novel anti-fibrotic mechanism of EPA, thereby suggesting a clinical implication for the treatment of NASH.
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