Document Detail

Analysis of hepatic genes involved in the metabolism of fatty acids and iron in nonalcoholic fatty liver disease.
MedLine Citation:
PMID:  19054139     Owner:  NLM     Status:  PubMed-not-MEDLINE    
AIMS: 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.
Hironori Mitsuyoshi; Kohichiroh Yasui; Yuichi Harano; Mio Endo; Kazuhiro Tsuji; Masahito Minami; Yoshito Itoh; Takeshi Okanoue; Toshikazu Yoshikawa
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Publication Detail:
Type:  Journal Article     Date:  2008-11-25
Journal Detail:
Title:  Hepatology research : the official journal of the Japan Society of Hepatology     Volume:  39     ISSN:  1386-6346     ISO Abbreviation:  Hepatol. Res.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-02     Completed Date:  2011-07-14     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  9711801     Medline TA:  Hepatol Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  366-73     Citation Subset:  -    
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