Lack of PPARα exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress

Toxicol Lett. 2011 Apr 10;202(1):23-9. doi: 10.1016/j.toxlet.2011.01.013. Epub 2011 Jan 22.


Peroxisome proliferator-activated receptor-α (PPARα) has been implicated in a potent anti-inflammatory activity. However, no information is available on whether PPARα can affect signal transducers and activator of transcription proteins (STATs) in acute liver damage. Thus, this study was aimed to investigate the in vivo role of PPARα in elevating STATs as well as oxidative/nitrosative stress in a model of lipopolysaccharide (LPS)-induced acute hepatic inflammatory injury. Using age-matched Ppara-null and wild-type (WT) mice, we demonstrate that the deletion of PPARα aggravates LPS-mediated liver injury through activating STAT1 and NF-κB-p65 accompanied by increased levels of pro-inflammatory cytokines. Furthermore, the activities of key anti-oxidant enzymes and mitochondrial complexes were significantly decreased while lipid peroxidation and protein nitration were elevated in LPS-exposed Ppara-null mice compared to WT. These results indicate that PPARα is important in preventing LPS-induced acute liver damage by regulating STAT1 inflammatory signaling pathways and oxidative/nitrosative stress.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Female
  • Lipopolysaccharides / toxicity*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Nitrosation / drug effects
  • Oxidative Stress / drug effects
  • PPAR alpha / metabolism*
  • STAT1 Transcription Factor / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects


  • Cytokines
  • Lipopolysaccharides
  • PPAR alpha
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Malondialdehyde