Rosiglitazone and bezafibrate modulate gene expression in a rat model of non-alcoholic fatty liver disease - A historical prospective

Hemda Schmilovitz-Weiss*, Edith Hochhauser, Michal Cohen, Yelena Chepurko, Smadar Yitzhaki, Grossman Ehud, Avshalom Leibowitz, Zvi Ackerman, Ziv Ben-Ari

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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. Method. 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-, PPAR-γ, and Mn superoxide dismutase2 (Mn SOD2). Western blot was used for proteins levels. Result: The FED rats showed a decrease in mRNA of MnSOD2, PPAR-, 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- 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- 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. Conclusion: A consistent reduction in hepatic expression of MnSOD2, PPAR- 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.

Original languageEnglish
Article number41
JournalLipids in Health and Disease
Volume12
Issue number1
DOIs
StatePublished - 2013

Keywords

  • Bezafibrate
  • Fructose enriched diet
  • Hepatic steatosis
  • Rosiglitazone

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