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.

Keywords: CMKLR1; Inflammation; TGFbeta; Triglycerides.