title: Resolvin E1 and chemerin C15 peptide do not improve rodent non-alcoholic steatohepatitis.
abstract: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease more commonly diagnosed in obesity. Therapeutic options to treat NASH are limited. Liver inflammation is a hallmark of NASH, and here it was tested whether the lipid mediator resolvin E1 (RvE1) and chemerin derived C15 peptide, which both exert potent anti-inflammatory activities, ameliorate NASH pathology. Male mice fed an atherogenic diet for 12 weeks, well described to induce NASH, received intraperitoneal injections of RvE1, C15 peptide or PBS as control for four days. Both treatments did not affect body weight or serum ALT. Liver triglycerides were neither reduced by the lipid nor the peptide. Hepatic expression of the macrophage marker F4/80 and the inflammatory mediators TNF and CCL2 was not changed. Further, fibrotic genes including TGFbeta, alphaSMA and CTGF were not affected by RvE1 or C15 injections. Serum adiponectin was comparable in the three groups. RvE1 and C15 are ligands of CMKLR1 whose expression was not reduced upon feeding the NASH inducing diet. This excludes low receptor levels as reason for therapeutic failure. In summary, current data demonstrate that RvE1 and chemerin derived C15 peptide do not ameliorate murine NASH.
authors: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors: Rebekka
authors: R
authors: Pohl
authors: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors: Lisa
authors: L
authors: Rein-Fischboeck
authors: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors: Elisabeth M
authors: EM
authors: Meier
authors: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors: Kristina
authors: K
authors: Eisinger
authors: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors: Sabrina
authors: S
authors: Krautbauer
authors: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany. Electronic address: christa.buechler@klinik.uni-regensburg.de.
authors: Christa
authors: C
authors: Buechler
mesh_terms: D000199:Actins / Q000235:genetics; D052242:Adiponectin / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000096:biosynthesis; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018925:Chemokines; D002630:Chemotactic Factors / Q000494:pharmacology*; D055513:Connective Tissue Growth Factor / Q000235:genetics; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D010455:Peptides / Q000494:pharmacology; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D000943:Antigens, Differentiation; C526318:CCN2 protein, mouse; C486456:CMKLR1 protein, mouse; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C523686:chemerin protein, mouse; C036763:monocyte-macrophage differentiation antigen; D055513:Connective Tissue Growth Factor; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid
keywords: CMKLR1; Inflammation; TGFbeta; Triglycerides