Retracted Article: Metabolomics reveals that PPARα activation protects against lithocholic acid-induced liver injury

Abstract

Some studies have reported that the activation of peroxisome proliferator-activated receptor alpha (PPARα) could protect against liver injury-induced by chemicals. In the present study, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOFMS)-based metabolomics revealed the protective effects of PPARα activation by fenofibrate on LCA-induced liver injury, which recovered metabolic disorder of bile acids in the enterohepatic system. Fenofibrate treatment significantly promoted the biosynthesis of phospholipids via the upregulation of expression levels of phospholipase A₂ g6, g7, and g12b (Pla₂ g6, g7, and g12b) in liver, contributing to the decrease in hepatic transforming growth factor beta (TGF-β) that regulates phospholipid homeostasis during liver injury. More importantly, the activation of PPARα by fenofibrate treatment protected against the enhanced expressions of the nuclear factor-kappa B (NF-κB) target genes, such as chemokine (C–C motif) ligand 2 (Ccl2) and secreted phosphoprotein 1 (Spp1). Its upstream factors related to NF-κB activation were also decreased by fenofibrate, including inflammasome, toll-like receptor (TLR), reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress. Taken together, the current study demonstrated that PPARα activation could show a protective effect against LCA-induced liver injury using a metabolomics approach.