Hepcidin and Iron Metabolism in Non-diabetic Obese and Type 2 Diabetic Rats

Summary： The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups： control group, non-diabetic obese group and type 2 dia- betic group （n=20 each）. The rats were evaluated physiologically and biochemically. The hepatic histo- pathological changes were observed using haematoxylin and eosin （HE） staining. The mRNA expres- sion patterns of hepcidin, interleukin-6 （IL-6）, hypoxia-inducible factor （HIF） and ferroportin （Fpn） in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further ana- lyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly （P〈0.001）. However, there was no significant difference in soluble transferring receptor （sTfR）：ferritin ratio among the three groups （P〉0.05）. The real-time RT-PCR, immunohistochemistry and Western blotting results all re- vealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group （P〈0.001）. The expression levels of hep- cidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant differ- ence （P〉0.05）. However, the protein expression levels of hepcidin in type 2 diabetic group were sig- nificantly higher than those in non-diabetic obese group （P〈0.05）. Compared to control group, the ex- pression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels ofFpn mRNA decreased （P〈0.05）. However, the expression lev- els ofHIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is substantially disturbed in non-diabetic obese and type 2 diabetic rats probably by the abnormal ex- pression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron re- lease from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.