Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease

Background: This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). Methods: We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient L-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNF alpha or IL1 beta. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. Results: The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase I gene during peroxisomal beta- oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001). Conclusion: Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. (C) 2017 Elsevier Inc. All rights reserved.