CDAHFD負荷マウス非アルコール性脂肪肝炎（NASH）モデルに対するペマフィブラート及びベザフィブラートの効果

抄録

In this study, 6-week-old mice were fed with a choline-deficient methionine-reduced high-fat diet (CDAHFD) for 6 and 12 weeks to confirm the development of the pathology of nonalcoholic steatohepatitis (NASH). The effects of pemafibrate (PF), a selective PPARα modulator, and bezafibrate (BF), PPAR-pan agonist were also evaluated on the progression of NASH pathology. Thus, the mice were given CDAHFD for 12weeks, with concomitant oral dose of 0.1, 0.3 mg/kg of PF, or 100 mg/kg of BF was administrated for 12 weeks. 

Serum and hepatic biomarkers (e.g., serum ALT, ornithine carbamoyl transferase (OCT), and hepatic TG) and hepatic mRNA expression of SREBP-1c, TNF-α, and Col1a1 were significantly increased in mice fed with CDAHFD for 6 weeks compared to control mice. In addition, mice fed with CDAHFD for an additional 6 weeks (12 weeks total) showed higher serum ALT, OCT, hepatic TC, hydroxyproline (HP), and hepatic mRNA expressions than mice fed CDAHFD for 6 weeks, revealing the development of NASH pathology.

100 mg/kg of BF administered by gavage for 12 weeks almost suppressed the progression of NASH pathology in CDAHFD fed mice. Administration of 0.1 and 0.3 mg/kg of PF suppressed the progression of NASH pathology as much as or better than administration of BF.

These findings showed that PF might thus be effective in preventing NASH.