Abstract

Excessive adiposity is associated with several metabolic perturbations including disturbances in iron homeostasis. Increased systemic inflammation in obesity stimulates expression of the iron regulatory hormone hepcidin, which can result in a maldistribution of bodily iron, which may be implicated in metabolic dysfunction. This study aimed to investigate the effect of adiposity and any associated inflammation on iron homeostasis and the potential implications of dysregulated iron metabolism on metabolic health. Analyses are based on a subsample from the cross-sectional Irish National Adult Nutrition Survey (2008–2010) (n = 1120). Ferritin status and risk of iron overload were determined based on established WHO ferritin ranges. Participants were classed as having a healthy % body fat or as having overfat or obesity based on age- and gender-specific % body fat ranges as determined by bioelectrical impedance. Biomarkers of iron status were examined in association with measures of body composition, serum adipocytokines and markers of metabolic health. Excessive % body fat was significantly associated with increased serum hepcidin and ferritin and an increased prevalence of severe risk of iron overload amongst males independent of dietary iron intake. Elevated serum ferritin displayed significant positive associations with serum triglycerides and markers of glucose metabolism, with an increased but non-significant presentation of metabolic risk factors amongst participants with overfat and obesity at severe risk of iron overload. Increased adiposity is associated with dysregulations in iron homeostasis, presenting as increased serum hepcidin, elevated serum ferritin and an increased risk of iron overload, with potential implications in impairments in metabolic health.

Highlights

  • Iron is an essential mineral, with integral roles in cellular respiration, DNA synthesis and cellular proliferation [1]

  • This study describes the iron status of a cohort of individuals classified as having either a healthy % BF or as having overfat or obesity using iron and inflammation associated biomarkers and investigates relationships between disturbed iron homeostasis and metabolic health

  • Results indicate that a higher % BF amongst males is associated with disturbances in iron homeostasis, presenting as elevated serum hepcidin and serum ferritin, with an increased prevalence of those at severe risk of iron overload

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Summary

Introduction

Iron is an essential mineral, with integral roles in cellular respiration, DNA synthesis and cellular proliferation [1]. Iron facilitates electron transfer and oxygen delivery in oxidation reduction reactions, which, while essential in maintaining normal cell metabolism, can result in the generation of toxic reactive oxygen species. A finely controlled balance between iron uptake, storage and utilisation is required to maintain iron homeostasis and ensure optimum functioning of metabolic processes. Hepcidin controls the absorption and transport of iron via the iron exporter ferroportin, which regulates intestinal absorption, cellular uptake and storage of iron in tissues [5]. Hepcidin synthesis is regulated by two major mechanisms: iron status and inflammatory stimuli. High circulating iron stimulates hepcidin expression, which induces cellular retention of iron, decreases intestinal absorption of iron and lowers concentrations of circulating free iron [6,7]

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