The specialized proresolving lipid mediator maresin 1 protects hepatocytes from lipotoxic and hypoxia‐induced endoplasmic reticulum stress

• DOI: 10.1096/fj.201700394r
• Publication Date: 2017-08-03T01:00:30Z
• Authors: Bibiana Rius; Marta Duran‐Güell; Roger Flores‐Costa; Cristina López‐Vi...; Aritz Lopategi; José Alcaraz‐Quiles; Mireia Casulleras; Juan José Lozano; Esther Titos; Joan Clària
• Keywords: Mediator; Hypoxia

Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are hallmarks non-alcoholic fatty liver disease (NAFLD), which is hepatic manifestation metabolic syndrome associated with obesity.The specialized pro-resolving lipid mediator maresin 1 (MaR1) preserves tissue homeostasis by exerting cytoprotective actions, dampening inflammation expediting its timely resolution.Here, we explored whether MaR1 protects cells from lipotoxic hypoxia-induced ER stress.Mice were rendered obese high-fat diet feeding experiments performed in primary hepatocytes, Kupffer precision-cut slices (PCLS).Palmitate-induced lipotoxicity increased altered autophagy effects that prevented MaR1.MaR1 protected hepatocytes against lipotoxicity-induced apoptosis activating UPR prosurvival mechanisms preventing excessive up-regulation pro-apoptotic pathways.Protective also seen challenged hypoxia TNFinduced cell death.High-throughput miRNA sequencing revealed actions specific signatures targeting both folding apoptosis.MaR1 lipotoxic-triggered PCLS.Of interest, enhanced phagocytic capacity.Together, these findings describe ability to oppose under conditions frequently encountered NAFLD.