Analysis of hepatic genes involved in the metabolism of fatty acids and iron in nonalcoholic fatty liver disease.
OBJECTIVE
Hepatic steatosis and iron cause oxidative stress, thereby progressing steatosis to steatohepatitis. We quantified the expression of genes involved in the metabolism of fatty acids and iron in patients with nonalcoholic fatty liver disease (NAFLD).


METHODS
The levels of transcripts for the following genes were quantified from biopsy specimens of 74 patients with NAFLD: thioredoxin (Trx), fatty acid transport protein 5 (FATP5), sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FASN), acetyl-coenzyme A carboxylase (ACAC), peroxisome proliferative activated receptor alpha (PPARalpha), cytochrome P-450 2E1 (CYP2E1), acyl-coenzyme A dehydrogenase (ACADM), acyl-coenzyme A oxidase (ACOX), microsomal triglyceride transfer protein (MTP), transferrin receptor 1 (TfR1), transferrin receptor 2 (TfR2) and hepcidin. Twelve samples of human liver RNA were used as controls. Histological evaluation followed the methods of Brunt.


RESULTS
The levels of all genes were significantly higher in the NAFLD patients than in controls. The Trx level increased as the stage progressed. The levels of FATP5, SREBP1c, ACAC, PPARalpha, CYP2E1, ACADM and MTP significantly decreased as the stage and grade progressed (P < 0.05). Hepatic iron score (HIS) increased as the stage progressed. The TfR1 level significantly increased as the stage progressed (P < 0.05), whereas TfR2 level significantly decreased (P < 0.05). The ratio of hepcidin mRNA/ferritin (P < 0.001) or hepcidin mRNA/HIS (P < 0.01) was significantly lower in NASH patients than simple steatosis patients.


CONCLUSIONS
Steatosis-related metabolism is attenuated as NAFLD progresses, whereas iron-related metabolism is exacerbated. Appropriate therapies should be considered on the basis of metabolic changes.
Mitsuyoshi
Hironori
H
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yasui
Kohichiroh
K
Harano
Yuichi
Y
Endo
Mio
M
Tsuji
Kazuhiro
K
Minami
Masahito
M
Itoh
Yoshito
Y
Okanoue
Takeshi
T
Yoshikawa
Toshikazu
T