title: Rosiglitazone and bezafibrate modulate gene expression in a rat model of non-alcoholic fatty liver disease--a historical prospective.
abstract: BACKGROUND
  Genetic factors implicated in the pathogenesis of non-alcoholic fatty liver disease are poorly understood. Our aim was to characterize three genes involved in a rat model of non-alcoholic fatty liver disease and investigate the effect of rosiglitazone and bezafibrate.
  
  
  METHODS
  Five rats were fed a chow diet (controls) and 18 a fructose-enriched diet (FED) for 5 weeks: 6 were administered rosiglitazone and 6 bezafibrate during the last 2 weeks and 6 were not treated at all. Livers were examined by reverse transcription-PCR for the genes encoding peroxisome proliferator-activated receptors (PPAR), PPAR-α, PPAR-γ, and Mn superoxide dismutase2 (Mn SOD2). Western blot was used for proteins levels.
  
  
  RESULTS
  The FED rats showed a decrease in mRNA of MnSOD2, PPAR-α, and PPAR-γ (3, 3.5 fold, and 27%, respectively) (p<0.05). The 3 genes normalized in response to rosiglitazone and bezafibrate. The proteins of MnSOD2, PPAR-α and PPAR-γ in the FED rats decreased (2.5, 2, and 2.2, respectively) (p<0.05). Following administration of rosiglitazone, proteins of MnSOD2, PPAR-α and PPAR-γ in the FED rats increased (reaching 1.5-fold, a 20% increase and normalization, respectively), (p<0.05). Administration of bezafibrate to the FED rats restored the proteins of 3 genes to baseline.
  
  
  CONCLUSIONS
  A consistent reduction in hepatic expression of MnSOD2, PPAR-α and PPAR-γ in the FED rats compared with controls was observed. Administration of either rosiglitazone or bezafibrate to the FED rats restored these genes to a pre-morbid state.
authors.affiliation: Division of Gastroenterology, Rabin Medical Center, Hasharon Hospital, Petach Tikva, Israel. hemdaw1@netvision.net.il
authors.forename: Hemda
authors.initials: H
authors.lastname: Schmilovitz-Weiss
authors.forename: Edith
authors.initials: E
authors.lastname: Hochhauser
authors.forename: Michal
authors.initials: M
authors.lastname: Cohen
authors.forename: Yelena
authors.initials: Y
authors.lastname: Chepurko
authors.forename: Smadar
authors.initials: S
authors.lastname: Yitzhaki
authors.forename: Ehud
authors.initials: E
authors.lastname: Grossman
authors.forename: Avshalom
authors.initials: A
authors.lastname: Leibowitz
authors.forename: Zvi
authors.initials: Z
authors.lastname: Ackerman
authors.forename: Ziv
authors.initials: Z
authors.lastname: Ben-Ari
mesh_terms: D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005632:Fructose; D015870:Gene Expression / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005632:Fructose; D013482:Superoxide Dismutase; D001629:Bezafibrate