title: Increased serum hepcidin levels in subjects with the metabolic syndrome: a population study.
abstract: The recent discovery of hepcidin, the key iron regulatory hormone, has changed our view of iron metabolism, which in turn is long known to be linked with insulin resistant states, including type 2 diabetes mellitus and the Metabolic Syndrome (MetS). Serum ferritin levels are often elevated in MetS (Dysmetabolic hyperferritinemia--DHF), and are sometimes associated with a true mild-to-moderate hepatic iron overload (dysmetabolic iron overload syndrome--DIOS). However, the pathophysiological link between iron and MetS remains unclear. This study was aimed to investigate, for the first time, the relationship between MetS and hepcidin at population level. We measured serum hepcidin levels by Mass Spectrometry in 1,391 subjects from the Val Borbera population, and evaluated their relationship with classical MetS features. Hepcidin levels increased significantly and linearly with increasing number of MetS features, paralleling the trend of serum ferritin. In multivariate models adjusted for relevant variables including age, C-Reactive Protein, and the HFE C282Y mutation, ferritin was the only significant independent predictor of hepcidin in males, while in females MetS was also independently associated with hepcidin. Overall, these data indicate that the fundamental iron regulatory feedback is preserved in MetS, i.e. that hepcidin tends to progressively increase in response to the increase of iron stores. Due to recently discovered pleiotropic effects of hepcidin, this may worsen insulin resistance and contribute to the cardiovascular complications of MetS.
authors.affiliation: Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Martinelli
authors.forename: Michela
authors.initials: M
authors.lastname: Traglia
authors.forename: Natascia
authors.initials: N
authors.lastname: Campostrini
authors.forename: Ginevra
authors.initials: G
authors.lastname: Biino
authors.forename: Michela
authors.initials: M
authors.lastname: Corbella
authors.forename: Cinzia
authors.initials: C
authors.lastname: Sala
authors.forename: Fabiana
authors.initials: F
authors.lastname: Busti
authors.forename: Corrado
authors.initials: C
authors.lastname: Masciullo
authors.forename: Daniele
authors.initials: D
authors.lastname: Manna
authors.forename: Sara
authors.initials: S
authors.lastname: Previtali
authors.forename: Annalisa
authors.initials: A
authors.lastname: Castagna
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pistis
authors.forename: Oliviero
authors.initials: O
authors.lastname: Olivieri
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000097:blood; D000071020:Hemochromatosis Protein; D064451:Hepcidins / Q000097:blood*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007501:Iron / Q000097:blood; D016014:Linear Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024821:Metabolic Syndrome / Q000097:blood* / Q000175:diagnosis; D008875:Middle Aged; D009154:Mutation; D011159:Population Surveillance / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D002097:C-Reactive Protein; D005293:Ferritins; D007501:Iron