Abstract
BackgroundExcess iron is associated with non-alcoholic steatohepatitis (NASH).ResultsmRNA expression of duodenal cytochrome b, divalent metal transporter 1, ferroportin 1, hepcidin, hephaestin and transferrin receptor 1 in liver were higher in high fat, high cholesterol-containing diet (HFCD) group than in normal diet (ND) group. mRNA levels of divalent metal transporter 1 and transferrin receptor 1, which stimulate iron absorption and excretion, were enhanced in small intestine. Epithelial mucosa of small intestine in HFCD group was characterized by plasma cell and eosinophil infiltration and increased vacuoles. Iron absorption was enhanced in this NASH model in the context of chronic inflammation of small intestinal epithelial cells, consequences of intestinal epithelial cell impairment caused by HFCD. Iron is transported to hepatocytes via portal blood, and abnormalities in iron absorption and excretion occur in small intestine from changes in iron transporter expression, which also occurs in NASH liver. Knockdown of hepcidin antimicrobial peptide led to enhanced heavy chain of ferritin expression in human hepatocytes, indicating association between hepcidin production and iron storage in hepatocytes.ConclusionsIron-related transporters in liver and lower/upper portions of small intestine play critical roles in NASH development.MethodsExpression of iron metabolism-related genes in liver and small intestine was analyzed in stroke-prone spontaneously hypertensive rats (SHR-SP), which develop NASH. Five-week-old SHR-SP fed ND or HFCD were examined. mRNA and protein levels of iron metabolism-related genes in liver and small intestine from 12- and 19-week-old rats were evaluated by real-time RT-PCR and immunohistochemistry or Western blot.
Highlights
The number of non-alcoholic steatohepatitis (NASH) cases and the number of cases with NASHassociated hepatocellular carcinoma (HCC) have increased [1,2,3,4]
In livers of the 19-week-old group, it is suggested that the increased expression of divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1), which are iron-related transporters, in the high fat and high cholesterolcontaining diet (HFCD) group enhanced the absorption and excretion of iron (Figure 2A)
Expression of the iron reductase gene duodenal cytochrome B (Dcytb) in the lower portion of the small intestine of the 19-week-old group was less in the HFCD group than in the 5-week-old group, and Dcytb expression tended to be less in the upper portion of the small intestine (Figure 2B)
Summary
The number of non-alcoholic steatohepatitis (NASH) cases and the number of cases with NASHassociated hepatocellular carcinoma (HCC) have increased [1,2,3,4]. MRNA levels of divalent metal transporter 1 and transferrin receptor 1, which stimulate iron absorption and excretion, were enhanced in small intestine. Iron is transported to hepatocytes via portal blood, and abnormalities in iron absorption and excretion occur in small intestine from changes in iron transporter expression, which occurs in NASH liver. Conclusions: Iron-related transporters in liver and lower/upper portions of small intestine play critical roles in NASH development. Methods: Expression of iron metabolism-related genes in liver and small intestine was analyzed in stroke-prone spontaneously hypertensive rats (SHR-SP), which develop NASH. MRNA and protein levels of iron metabolism-related genes in liver and small intestine from 12- and 19-week-old rats were evaluated by real-time RT-PCR and immunohistochemistry or Western blot Five-week-old SHR-SP fed ND or HFCD were examined. mRNA and protein levels of iron metabolism-related genes in liver and small intestine from 12- and 19-week-old rats were evaluated by real-time RT-PCR and immunohistochemistry or Western blot
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