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Issue 79, 2017, Issue in Progress
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Metabolomics reveals that PPARα activation protects against lithocholic acid-induced liver injury

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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.

Graphical abstract: Metabolomics reveals that PPARα activation protects against lithocholic acid-induced liver injury

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Publication details

The article was received on 09 Aug 2017, accepted on 17 Oct 2017 and first published on 26 Oct 2017


Article type: Paper
DOI: 10.1039/C7RA08823J
Citation: RSC Adv., 2017,7, 49849-49857
  • Open access: Creative Commons BY license
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    Metabolomics reveals that PPARα activation protects against lithocholic acid-induced liver injury

    Q. Zhao, R. Yang, F. Liu, J. Wang, D. Hu, X. Yang and F. Li, RSC Adv., 2017, 7, 49849
    DOI: 10.1039/C7RA08823J

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