Hepcidin response to acute iron intake and chronic iron loading in dysmetabolic iron overload syndrome

Liver Int. 2011 Aug;31(7):994-1000. doi: 10.1111/j.1478-3231.2011.02520.x. Epub 2011 Apr 18.

Abstract

Background: The pathogenesis of dysmetabolic iron overload syndrome (DIOS) is still unclear. Hepcidin is the key regulator of iron homeostasis controlling iron absorption and macrophage release.

Aim: To investigate hepcidin regulation by iron in DIOS.

Methods: We analysed urinary hepcidin at baseline and 24 h after a 65 mg oral iron dose in 24 patients at diagnosis and after iron depletion (n = 13) and compared data with those previously observed in 23 healthy controls. Serum iron indices, liver histology and metabolic data were available for all patients.

Results: At diagnosis, hepcidin values were significantly higher than in controls (P < 0.001). After iron depletion, hepcidin levels decreased to normal values in all patients. At baseline, a significant response of hepcidin to iron challenge was observed only in the subgroup with lower basal hepcidin concentration (P = 0.007). In iron-depleted patients, urinary hepcidin significantly increased after oral iron test (P = 0 .006).

Conclusions: Ours findings suggest that in DIOS, the progression of iron accumulation is counteracted by the increase in hepcidin production and progressive reduction of iron absorption, explaining why these patients develop a mild-moderate iron overload that tends to a plateau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Alanine Transaminase / blood
  • Antimicrobial Cationic Peptides / metabolism*
  • Antimicrobial Cationic Peptides / urine
  • Blood Glucose / analysis
  • C-Reactive Protein / analysis
  • Cholesterol / blood
  • DNA Mutational Analysis
  • Female
  • Hemochromatosis Protein
  • Hemoglobins / analysis
  • Hepcidins
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Insulin / blood
  • Iron / administration & dosage
  • Iron / metabolism*
  • Iron Overload / metabolism*
  • Iron Overload / physiopathology*
  • Italy
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Membrane Proteins / genetics
  • Statistics, Nonparametric
  • Triglycerides / blood
  • gamma-Glutamyltransferase / blood

Substances

  • Antimicrobial Cationic Peptides
  • Blood Glucose
  • HAMP protein, human
  • HFE protein, human
  • Hemochromatosis Protein
  • Hemoglobins
  • Hepcidins
  • Histocompatibility Antigens Class I
  • Insulin
  • Membrane Proteins
  • Triglycerides
  • C-Reactive Protein
  • Cholesterol
  • Iron
  • gamma-Glutamyltransferase
  • Alanine Transaminase