The FASEB journal, 2017-12, Vol.31 (12), p.5384-5398
2017
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- Autor(en) / Beteiligte
- Titel
- The specialized proresolving lipid mediator maresin 1 protects hepatocytes from lipotoxic and hypoxia‐induced endoplasmic reticulum stress
- Ist Teil von
- The FASEB journal, 2017-12, Vol.31 (12), p.5384-5398
- Ort / Verlag
- United States: Federation of American Societies for Experimental Biology
- Erscheinungsjahr
- 2017
- Quelle
- Wiley Online Library - AutoHoldings Journals
- Beschreibungen/Notizen
- ABSTRACT Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are hallmarks of nonalcoholic fatty liver disease (NAFLD), which is the hepatic manifestation of the metabolic syndrome associated with obesity. The specialized proresolving lipid mediator maresin 1 (MaR1) preserves tissue homeostasis by exerting cytoprotective actions, dampening inflammation, and expediting its timely resolution. Here, we explored whether MaR1 protects liver cells from lipotoxic and hypoxia‐induced ER stress. Mice were rendered obese by high‐fat diet feeding, and experiments were performed in primary hepatocytes, Kupffer cells, and precision‐cut liver slices (PCLSs). Palmitate‐induced lipotoxicity increased ER stress and altered autophagy in hepatocytes, effects that were prevented by MaR1. MaR1 protected hepatocytes against lipotoxicity‐induced apoptosis by activating the UPR prosurvival mechanisms and preventing the excessive up‐regulation of proapoptotic pathways. Protective MaR1 effects were also seen in hepatocytes challenged with hypoxia and TNF‐α‐induced cell death. High‐throughput microRNA (miRNA) sequencing revealed that MaR1 actions were associated with specific miRNA signatures targeting both protein folding and apoptosis. MaR1 also prevented lipotoxic‐triggered ER stress and hypoxia‐induced inflammation in PCLSs and enhanced Kupffer cell phagocytic capacity. Together, these findings describe the ability of MaR1 to oppose ER stress in liver cells under conditions frequently encountered in NAFLD.—Rius, B., Duran‐Güell, M., Flores‐Costa, R., López‐Vicario, C., Lopategi, A., Alcaraz‐Quiles, J., Casulleras, M., Lozano, J. J., Titos, E., Clària, J. The specialized proresolving lipid mediator maresin 1 protects hepatocytes from lipotoxic and hypoxia‐induced endoplasmic reticulum stress. FASEB J. 31, 5384–5398 (2017). www.fasebj.org
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0892-6638eISSN: 1530-6860DOI: 10.1096/fj.201700394RTitel-ID: cdi_proquest_miscellaneous_1925892358
- Format
- –
- Schlagworte
- Animals, Antigens, Ly - genetics, Antigens, Ly - metabolism, Apoptosis, Apoptosis - genetics, Apoptosis - physiology, Autophagy, Cell death, Diet, High-Fat - adverse effects, Endoplasmic reticulum, Endoplasmic Reticulum Stress - genetics, Endoplasmic Reticulum Stress - physiology, Fatty liver, Hepatocytes, Hepatocytes - metabolism, High fat diet, Homeostasis, Hypoxia, Hypoxia - metabolism, Kupffer cells, Kupffer Cells - metabolism, Lipids, Liver, Liver - metabolism, liver cells, Liver diseases, Male, Metabolic syndrome, Mice, Mice, Inbred C57BL, MicroRNAs - metabolism, miRNA, NAFLD, Natural Cytotoxicity Triggering Receptor 1 - genetics, Natural Cytotoxicity Triggering Receptor 1 - metabolism, Non-alcoholic Fatty Liver Disease - metabolism, Obesity, Obesity - metabolism, Palmitic acid, Phagocytes, Phagocytosis, Protein folding, Ribonucleic acid, RNA, Rodents, Stress, Stresses, Tumor Necrosis Factor-alpha - metabolism, Tumor necrosis factor-α, UPR