Abstract 13091: Pemafibrate Reduced Hepatic Fibrosis and Cardiac Inflammation in Cholesterol-dominant, Atherogenic-Diet Induced Steatohepatitis Model in Mice

Abstract

Introduction: Pemafibrate reduces serum triglycerides level and has been reported that it also decreased hepatic triglycerides. In recent decades, the number of patients with nonalcoholic fatty liver diseases has increased and it has become a problem that the patients with steatohepatitis would develop cardiovascular diseases. Aim: The aim of this study is to analyze the effect of pemafibrate on hepatic inflammation and cardiac function in a diet-induced steatohepatitis model. Methods: C57Bl/6 wild mice were administered cholesterol-loading atherogenic-diet (Cont group) or the one with pemafibrate 0.1 mg/kg (Pema group) for 3 or 8 weeks, respectively. Serum lipids, hepatic inflammatory cytokines, histology, gene expression, lipid contents, and cardiac magnetic resonance imaging (MRI) were investigated. Left ventricular strain was analyzed by workstation of ENTORRES©. Results: In Pema group, serum HDL-C level was increased, non-HDL-C level was decreased. serum TNFα was decreased (82.0±10.8 v.s. 48.0±2.1, p<0.0001). In liver, gene expression of TNFa, Il1b, Il6, Tgfb, Col1a, Col2a showed marked reduction. In HE staining, destruction of the hepatic lobule structure was improved. F4/80 staining demonstrated marked reduction of macrophage infiltration. In Tunel staining, apoptosis cell was suppressed. Liver lipid extraction study showed total cholesterol and free cholesterol were decreased by 50%. MRI scanning demonstrated that heterogeneous attenuation of longitudinal strain of left ventricular (Figure). Conclusion: Pemafibrate suppresses liver inflammation and inhibit left ventricular dysfunction caused by cholesterol-rich-atherogenic diet.