Risk of Iron Overload in Obesity and Implications in Metabolic Health

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.

Keywords: body fat; ferritin; hepcidin; inflammation; iron overload; metabolic health.

Figure 1

The relationship between % body fat category and (A,B) WHO iron status category as determined by ferritin and (C,D) HEIRS ferritin status. *** p < 0.001 (Bonferroni correction). X² test of categorical variables, with data presented as % study population. % BF = percentage body fat. P w overfat/obesity = people with overfat/obesity, I-S = iron stores, and I-O = iron overload.

Figure 2

Indices of metabolic health between iron status groups across all categories of BF %: (A) serum triglycerides (mmol/L), (B) serum direct HDL cholesterol (mmol/L), (C) serum insulin (µIU/mL), and (D) Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).* p < 0.05. ANCOVA of log10-transformed variables (covariates = age, gender, contraception use, and smoking status). Data are presented as the median and IOR. BF % = body fat percentage. P w overfat/obesity = people with overfat/obesity, I-S = iron stores, and I-O = iron overload.