Journal Article

Increased Serum Hepcidin Levels in Subjects with the Metabolic Syndrome: A Population Study

Masciullo, Corrado, Pistis, Giorgio, Martinelli, Nicola, Campostrini, Natascia, Biino, Ginevra, Toniolo, Daniela, Camaschella, Clara, Previtali, Sara, Olivieri, Oliviero, Corbella, Michela, Girelli, Domenico, Sala, Cinzia, Castagna, Annalisa, Traglia, Michela, Manna, Daniele, Busti, Fabiana

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Analysis / Analysis of Variance / Biology / Blood pressure / C-reactive protein / C-Reactive Protein - metabolism / Complications / Cytokines / Diabetes / Diabetes mellitus / Female / Females / Ferritin / Ferritins - blood / Hemochromatosis Protein / Hepcidin / Hepcidins - blood / Histocompatibility Antigens Class I - genetics / Homeostasis / Humans / Insulin / Insulin resistance / Iron / Iron - blood / Linear Models / Liver diseases / Male / Males / Mass spectrometry / Mass spectroscopy / Medical research / Medicine / Membrane Proteins - genetics / Metabolic disorders / Metabolic syndrome / Metabolic Syndrome - blood / Metabolic Syndrome - diagnosis / Metabolism / Middle Aged / Mutation / Obesity / Physiological aspects / Population / Population studies / Population Surveillance - methods / Population-based studies / Predictive Value of Tests / Prognosis / Rodents / Studies / Substance abuse treatment / Triglycerides / Type 2 diabetes / Variance analysis / Womens health