9-PAHSA Prevents Mitochondrial Dysfunction and Increases the Viability of Steatotic Hepatocytes.

Autor: Schultz Moreira AR; Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany., Rüschenbaum S; Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany., Schefczyk S; Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany., Hendgen-Cotta U; West German Heart and Vascular Center, Department of Cardiology and Vascular Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Rassaf T; West German Heart and Vascular Center, Department of Cardiology and Vascular Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Broering R; Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany., Hardtke-Wolenski M; Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.; Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, 30625 Hannover, Germany., Buitrago-Molina LE; Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.; Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 Nov 05; Vol. 21 (21). Date of Electronic Publication: 2020 Nov 05.
DOI: 10.3390/ijms21218279
Abstrakt: Nonalcoholic fatty liver disease (NAFLD) is quickly becoming the most common liver disease worldwide. Within the NAFLD spectrum, patients with nonalcoholic steatohepatitis (NASH) are at the highest risk of developing cirrhosis and disease progression to hepatocellular carcinoma. To date, therapeutic options for NASH patients have been ineffective, and therefore, new options are urgently needed. Hence, a model system to develop new therapeutic interventions is needed. Here, we introduce two new in vitro models of steatosis induction in HepG2 cells and primary murine hepatocytes. We used a recently discovered novel class of bioactive anti-inflammatory lipids called branched fatty acid esters of hydroxyl fatty acids. Among these bioactive lipids, palmitic-acid-9-hydroxy-stearic-acid (9-PAHSA) is the most promising as a representative nondrug therapy based on dietary supplements or nutritional modifications. In this study, we show a therapeutic effect of 9-PAHSA on lipotoxicity in steatotic primary hepatocytes and HepG2 cells. This could be shown be increased viability and decreased steatosis. Furthermore, we could demonstrate a preventive effect in HepG2 cells. The outcome of 9-PAHSA administration is both preventative and therapeutically effective for hepatocytes with limited damage. In conclusion, bioactive lipids like 9-PAHSA offer new hope for prevention or treatment in patients with fatty liver and steatosis.
Databáze: MEDLINE
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