Abstract
Objective
Excess iron deposition in tissues leads to increased oxidative stress. The clinical
observation that non-alcoholic fatty liver disease (NAFLD) is frequently associated
with hepatic iron overload (HIO) indicates that iron-induced oxidative stress may
be related to NAFLD pathology. Decreased expression of hepcidin, a hepatic hormone
that suppresses dietary iron absorption in the duodenum, is frequently observed in
NAFLD patients and has been postulated to be a cause of HIO.
Materials/Methods
Because dietary fat and fructose intake play roles in the onset of NAFLD, we fed C57BL/6J
mice a high-fat, high-fructose (HFHFr) diet for 16 weeks to study the relationship between hepatic iron content and NAFLD.
Results
Within 4 weeks after the start of the experiment, the mice exhibited significant increases
in hepatic free fatty acid (FFA) content, serum insulin levels, and the homeostasis
model assessment of insulin resistance. Interestingly, hepatic iron content and oxidative
stress significantly increased with the HFHFr diet 2 weeks earlier than hepatic FFA accumulation and decreased insulin sensitivity. Moreover,
hepatic hepcidin expression was significantly downregulated, as is also observed in
NAFLD patients, but much later than the onset of HIO.
Conclusions
Accordingly, our data demonstrated that HIO may have a pathogenic role in the onset
of liver steatosis and insulin resistance. Moreover, distinct mechanisms, in addition
to hepcidin, may underlie NAFLD-related HIO. These data suggest that the HFHFr diet
can be used for establishing a suitable model to study the precise mechanism of HIO
in NAFLD patients.
Abbreviations:
ALT (alanine aminotransferase), AST (aspartate aminotransferase), FFA (free fatty acid), HFHFr (high-fat, high-fructose diet), HIO (hepatic iron overload), HOMA-IR (homeostasis model assessment of insulin resistance), JNK (c-Jun N-terminal kinase), NAFLD (non-alcoholic fatty liver disease), TG (triglyceride)Keywords
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Article info
Publication history
Published online: August 01, 2012
Accepted:
June 26,
2012
Received:
February 29,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
