title: Hepcidin resistance in dysmetabolic iron overload.
abstract: Dysmetabolic iron overload syndrome (DIOS) is a frequent condition predisposing to metabolic, cardiovascular and hepatic damage, whose pathogenesis remains poorly defined. Aim of this study was to characterize iron metabolism in DIOS.
  
  
  
  We evaluated 18 patients with DIOS, compared to 18 with nonalcoholic fatty liver and 23 healthy individuals with normal iron status, and 10 patients with hereditary haemochromatosis by a 24-h oral iron tolerance test with hepcidin measurement and iron metabolism modelling under normal iron stores.
  
  
  
  Dysmetabolic iron overload syndrome patients had higher peak transferrin saturation and area under the-curve of transferrin saturation than subjects with normal iron status, but lower values than haemochromatosis patients (P < 0.05 for all). Conversely, they had higher peak circulating hepcidin levels and area under the curve of hepcidin than the other groups (P < 0.05 for all). This was independent age, sex, haemoglobin, ferritin, and transferrin saturation levels (P = 0.0002). Hepcidin increase in response to the rise in transferrin saturation (hepcidin release index) was not impaired in DIOS patients. Viceversa, the ability of the hepcidin spike to control the rise in transferrin saturation at the beginning of the test (hepcidin resistance index) was impaired in DIOS (P = 0.0002). In DIOS patients, the hepcidin resistance index was correlated with ferritin levels at diagnosis (P = 0.016).
  
  
  
  Dysmetabolic iron overload syndrome is associated with a subtle impairment in the ability of the iron hormone hepcidin to restrain iron absorption following an iron challenge, suggesting a hepcidin resistance state. Further studies are required to better characterize the molecular mechanism underpinning this new iron metabolism alteration.
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Rametta
authors.affiliation: Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Dongiovanni
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pelusi
authors.affiliation: Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Francione
authors.affiliation: Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Iuculano
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Borroni
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Fatta
authors.affiliation: Policlinico G.B. Rossi, Department of Medicine, Università di Verona, Verona, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Castagna
authors.affiliation: Policlinico G.B. Rossi, Department of Medicine, Università di Verona, Verona, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.|Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. luca.valenti@unimi.it.|Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy. luca.valenti@unimi.it.
authors.forename: Luca
authors.identifier: 0000-0001-8909-0345
authors.initials: L
authors.lastname: Valenti
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005293:Ferritins / Q000097:blood*; D006432:Hemochromatosis / Q000150:complications*; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism / Q000503:physiopathology*; D007558:Italy; D016014:Linear Models; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D064451:Hepcidins; D005293:Ferritins; D007501:Iron
keywords: hereditary haemochromatosis; iron; liver; nonalcoholic fatty liver disease