title: Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection.
abstract: OBJECTIVE
  Liver inflammation, fibrosis, and dyslipidemia are common features in patients with chronic hepatitis C virus (HCV) infection. Because peroxisome proliferator-activated receptor alpha (PPARalpha) is highly expressed in the liver and is involved in the regulation of lipid metabolism and inflammation, we sought to determine whether HCV infection may locally impair PPARalpha expression and activity.
  
  
  METHODS
  PPARalpha expression was investigated in liver biopsy specimens of 86 untreated patients with HCV infection and controls, by using real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. PPARalpha activity was assessed by quantification of the key gene target carnitine palmitoyl acyl-CoA transferase 1 (CPT1A) messenger RNA (mRNA). The influence of HCV core protein on PPARalpha mRNA expression was analyzed in vitro by real-time PCR in HCV core-expressing HepG2 cells activated with the PPARalpha ligand fenofibric acid.
  
  
  RESULTS
  Hepatic concentrations of PPARalpha and CPT1A expressed by hepatocytes were impaired profoundly in the livers of untreated patients with HCV infection compared with controls. A mean decrease of 85% in PPARalpha mRNA expression paralleled with a lack of CPT1A mRNA induction also were observed in HCV core-expressing HepG2 cells compared with controls.
  
  
  CONCLUSIONS
  HCV infection is related to altered expression and function of the anti-inflammatory nuclear receptor PPARalpha. These results identify hepatic PPARalpha as one mechanism underlying the pathogenesis of HCV infection, and as a new therapeutic target in traditional treatment of HCV-induced liver injury.
authors.affiliation: Equipe Mixte INSERM 0114, Centre Hospitalier Universitaire, Lille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dharancy
authors.forename: Mathilde
authors.initials: M
authors.lastname: Malapel
authors.forename: Gabriel
authors.initials: G
authors.lastname: Perlemuter
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.forename: Yang
authors.initials: Y
authors.lastname: Cheng
authors.forename: Laurent
authors.initials: L
authors.lastname: Dubuquoy
authors.forename: Philippe
authors.initials: P
authors.lastname: Podevin
authors.forename: Filoména
authors.initials: F
authors.lastname: Conti
authors.forename: Valérie
authors.initials: V
authors.lastname: Canva
authors.forename: David
authors.initials: D
authors.lastname: Philippe
authors.forename: Luc
authors.initials: L
authors.lastname: Gambiez
authors.forename: Philippe
authors.initials: P
authors.lastname: Mathurin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Paris
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
mesh_terms: D001706:Biopsy; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D017931:DNA Primers; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms; D047493:PPAR alpha / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D017931:DNA Primers; D047493:PPAR alpha; C006012:fenofibric acid; D011345:Fenofibrate