ArticleDisease models & mechanisms2020
Novel defatting strategies reduce lipid accumulation in primary human culture models of liver steatosis.
Article in Disease models & mechanisms, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
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- IPMK modulates FFA-induced insulin resistance in primary mouse hepatocytes.bioRxiv : the preprint server for biology · 2023Article
- Experimental Models for Studying Structural and Functional State of the Pathological Liver (Review).Sovremennye tekhnologii v meditsine · 2023Review
- The necroptosis-inducing pseudokinase mixed lineage kinase domain-like regulates the adipogenic differentiation of pre-adipocytes.iScience · 2022Article
- A Review of Defatting Strategies for Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2022Review
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- Best Practices and Progress in Precision-Cut Liver Slice Cultures.International journal of molecular sciences · 2021Review
- RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic.International journal of molecular sciences · 2021Article
- Target Therapies for NASH/NAFLD: From the Molecular Aspect to the Pharmacological and Surgical Alternatives.Journal of personalized medicine · 2021Review
- Defatting strategies in the current era of liver steatosis.JHEP reports : innovation in hepatology · 2021Review
- Ex-Vivo Pharmacological Defatting of the Liver: A Review.Journal of clinical medicine · 2021Review
- In Vitro and In Vivo Models of Non-Alcoholic Fatty Liver Disease: A Critical Appraisal.Journal of clinical medicine · 2020Review
- Necroptosis in Hepatosteatotic Ischaemia-Reperfusion Injury.International journal of molecular sciences · 2020Review
- Cold-Atmospheric Plasma Induces Tumor Cell Death in Preclinical In Vivo and In Vitro Models of Human Cholangiocarcinoma.Cancers · 2020Article
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15 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Normothermic perfusion provides a means to rescue steatotic liver grafts, including by pharmacological defatting. In this study, we tested the potential of new drug combinations to trigger defatting in three human culture models, primary hepatocytes with induced steatosis, primary hepatocytes isolated from steatotic liver, and precision-cut liver slices (PCLS) of steatotic liver. Forskolin, L-carnitine and a PPARα agonist were all combined with rapamycin, an immunosuppressant that induces autophagy, in a D-FAT cocktail. D-FAT was tested alone or in combination with necrosulfonamide, an inhibitor of mixed lineage kinase domain like pseudokinase involved in necroptosis. Within 24 h, in all three models, D-FAT induced a decrease in triglyceride content by 30%, attributable to an upregulation of genes involved in free fatty acid β-oxidation and autophagy, and a downregulation of those involved in lipogenesis. Defatting was accompanied by a decrease in endoplasmic reticulum stress and in the production of reactive oxygen species. The addition of necrosulfonamide increased the efficacy of defatting by 8%-12% in PCLS, with a trend towards increased autophagy. In conclusion, culture models, notably PCLS, are insightful to design strategies for liver graft rescue. Defatting can be rapidly achieved by combinations of drugs targeting mitochondrial oxidative metabolism, macro-autophagy and lipogenesis.
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