Document Detail

Interstrain differences in the progression of nonalcoholic steatohepatitis to fibrosis in mice are associated with altered hepatic iron metabolism.
MedLine Citation:
PMID:  25256357     Owner:  NLM     Status:  Publisher    
Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide. Currently, there is a lack of conclusive information to clarify the molecular events and mechanisms responsible for the progression of NAFLD to fibrosis and cirrhosis and, more importantly, for differences in interindividual disease severity. The aim of this study was to investigate a role of interindividual differences in iron metabolism among inbred mouse strains in the pathogenesis and severity of fibrosis in a model of NAFLD. Feeding male A/J, 129S1/SvImJ and WSB/EiJ mice a choline- and folate-deficient diet caused NAFLD-associated liver injury and iron metabolism abnormalities, especially in WSB/EiJ mice. NAFLD-associated fibrogenesis was correlated with a marked strain- and injury-dependent increase in the expression of iron metabolism genes, especially transferrin receptor (Tfrc), ferritin heavy chain (Fth1), and solute carrier family 40 (iron-regulated transporter), member 1 (Slc40a1, Fpn1) and their related proteins, and pronounced down-regulation of the iron regulatory protein 1 (IRP1), with the magnitude being A/J<129S1/SvImJ<WSB/EiJ. Mechanistically, down-regulation of IRP1 was linked to an increased expression of microRNAs miR-200a and miR-223, which was negatively correlated with IRP1. The results of this study demonstrate that the interstrain variability in the extent of fibrogenesis was associated with a strain-dependent deregulation of hepatic iron homeostasis.
Svitlana Shpyleva; Marta Pogribna; Christy Cozart; Matthew S Bryant; Levan Muskhelishvili; Volodymyr P Tryndyak; Sharon A Ross; Frederick A Beland; Igor P Pogribny
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-19
Journal Detail:
Title:  The Journal of nutritional biochemistry     Volume:  -     ISSN:  1873-4847     ISO Abbreviation:  J. Nutr. Biochem.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-9-26     Completed Date:  -     Revised Date:  2014-9-27    
Medline Journal Info:
Nlm Unique ID:  9010081     Medline TA:  J Nutr Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Published by Elsevier Inc.
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