Hepcidin and iron metabolism in non-diabetic obese and type 2 diabetic rats.

Yue Chen, Hui-Qing Yin, Hao-Ling Liu, Lei Xiu, Xiao-Yu Peng
Author Information
  1. Yue Chen: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  2. Hui-Qing Yin: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. yinhuiqing2003@gmail.com.
  3. Hao-Ling Liu: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  4. Lei Xiu: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  5. Xiao-Yu Peng: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

Abstract

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 diabetic group (n=20 each). The rats were evaluated physiologically and biochemically. The hepatic histopathological changes were observed using haematoxylin and eosin (HE) staining. The mRNA expression 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 analyzed 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 revealed 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 hepcidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant difference (P>0.05). However, the protein expression levels of hepcidin in type 2 diabetic group were significantly higher than those in non-diabetic obese group (P<0.05). Compared to control group, the expression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels of Fpn mRNA decreased (P<0.05). However, the expression levels of HIF 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 expression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron release from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.

Keywords

References

  1. Diabetes Care. 2005 Aug;28(8):2061-3 [PMID: 16043762]
  2. Eur Rev Med Pharmacol Sci. 2012 Oct;16(10):1441-5 [PMID: 23104663]
  3. Int J Obes (Lond). 2007 Sep;31(9):1412-9 [PMID: 17438557]
  4. J Biol Chem. 2000 Jun 30;275(26):19906-12 [PMID: 10747949]
  5. Haematologica. 2012 Nov;97(11):1648-56 [PMID: 22581006]
  6. Nepal Med Coll J. 2014 Sep;16(1):54-7 [PMID: 25799813]
  7. Mol Biol Cell. 2007 Jul;18(7):2569-78 [PMID: 17475779]
  8. BMC Med. 2012 Oct 10;10:119 [PMID: 23046549]
  9. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14 [PMID: 19896746]
  10. Mol Cell. 2000 Feb;5(2):299-309 [PMID: 10882071]
  11. Diab Vasc Dis Res. 2014 May 22;11(4):270-280 [PMID: 24853909]
  12. Hepatology. 1981 Sep-Oct;1(5):431-5 [PMID: 7308988]
  13. Am J Epidemiol. 2007 May 1;165(9):1047-54 [PMID: 17284722]
  14. Gastroenterology. 1988 Oct;95(4):1056-62 [PMID: 3410220]
  15. J Am Soc Nephrol. 2005 Oct;16(10):3070-80 [PMID: 16033854]
  16. J Clin Invest. 2004 May;113(9):1271-6 [PMID: 15124018]
  17. JAMA. 2004 Feb 11;291(6):711-7 [PMID: 14871914]
  18. Clin Endocrinol (Oxf). 2003 Mar;58(3):380-5 [PMID: 12608945]
  19. J Hepatol. 2011 Oct;55(4):920-32 [PMID: 21718726]
  20. Nature. 2000 Feb 17;403(6771):776-81 [PMID: 10693807]
  21. Int J Environ Res Public Health. 2014 Mar 28;11(4):3586-98 [PMID: 24686488]
  22. Rev Endocr Metab Disord. 2015 Mar;16(1):15-23 [PMID: 25520048]
  23. Int J Med Sci. 2013 Aug 22;10(10):1412-21 [PMID: 23983604]
  24. Biochim Biophys Acta. 2009 Jul;1790(7):671-81 [PMID: 18501198]
  25. Hepatology. 2012 Feb;55(2):622-33 [PMID: 22120903]
  26. Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G199-203 [PMID: 16407589]
  27. Biosci Rep. 2015 Mar 31;35(3):null [PMID: 26182354]

MeSH Term

Animals
Diabetes Mellitus, Type 2
Hepcidins
Interleukin-6
Iron
Male
Obesity
RNA, Messenger
Rats
Rats, Wistar
Real-Time Polymerase Chain Reaction

Chemicals

Hepcidins
Interleukin-6
RNA, Messenger
Iron

Word Cloud

Created with Highcharts 10.0.0groupexpressionnon-diabetic2diabetictypeobesehepcidinlevelsironcontrolmRNAmetabolismratssignificantlyP<005FpnincreasedHoweversignificantdifferencechangeshepaticratpatternsIL-6HIFliveranalyzedreal-timeRT-PCRproteinimmunohistochemistryWesternblottingcompared001amongthreegroupsP>0probablyaimstudyinvestigateregulatorymoleculesinvolvedobese/typemodelsMaleWistardivided3groups:n=20evaluatedphysiologicallybiochemicallyhistopathologicalobservedusinghaematoxylineosinHEstaininginterleukin-6hypoxia-induciblefactorferroportinferritinsolubletransferringreceptorsTfR:ferritinratioresultsrevealedelevatedshowedhigherCompareddecreasedsuggestedsubstantiallydisturbedabnormalchronicinflammatorystatusmayrestrainreleasecellsaffectingassociatesdevelopmentcomplicationHepcidinobesitydiabetes

Similar Articles

Cited By