Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, reduces hepatic steatosis and lipid peroxidation in fatty liver Shionogi mice with hereditary fatty liver.
OBJECTIVE
The fatty liver Shionogi (FLS) mouse, a unique model for nonalcoholic fatty liver disease (NAFLD), is an inbred strain that develops spontaneous hepatic steatosis without obesity or diabetes mellitus. Peroxisome proliferator-activated receptor (PPAR) alpha controls fatty acid metabolism. In the present study, we investigated the effect of fenofibrate, a PPARalpha agonist, on hepatic steatosis in FLS mice.


METHODS
Thirteen-week-old FLS mice were fed a diet with 0.1% fenofibrate (w/w) for 12 days. The degree of hepatic steatosis was estimated by histological examination and hepatic triglyceride levels. Expression levels of genes involved in fatty acid turnover, including Acox1, Cpt1a, Fabp1, Acadl, and Acadm, were determined by Northern blot analyses. We measured levels of lipid peroxidation, glutathione, and anti-oxidative enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, in the liver.


RESULTS
Treatment of FLS mice with fenofibrate improved hepatic steatosis by activating expression of genes involved in fatty acid turnover and decreased hepatic lipid peroxidation. Fenofibrate increased the activity of catalase by upregulating its mRNA levels.


CONCLUSIONS
Fenofibrate, which is currently used in therapy of hyperlipidemia, might also be useful for treating patients with NAFLD even in cases where NAFLD is not associated with obesity or diabetes mellitus.
Harano
Yuichi
Y
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yasui
Kohichiroh
K
Toyama
Tetsuya
T
Nakajima
Tomoki
T
Mitsuyoshi
Hironori
H
Mimani
Masahito
M
Hirasawa
Tsutomu
T
Itoh
Yoshito
Y
Okanoue
Takeshi
T
D000818:Animals; D002374:Catalase / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D051379:Mice; D008817:Mice, Mutant Strains; D047493:PPAR alpha / Q000819:agonists*; D012333:RNA, Messenger / Q000032:analysis
D005227:Fatty Acids; D047493:PPAR alpha; D012333:RNA, Messenger; D002374:Catalase; D011345:Fenofibrate