Overweight children have higher circulating hepcidin concentrations and lower iron status but have dietary iron intakes and bioavailability comparable with normal weight children

Abstract

Background: Obesity increases the risk for iron deficiency, but the underlying mechanism is unclear. It is possible that overweight individuals may have lower dietary iron intake and/or bioavailability. Alternatively, obesity-related inflammation may increase hepcidin concentrations and reduce iron availability. Circulating hepcidin levels have not been compared in normal weight vs overweight individuals. Objective: The objective of this study was to compare iron status, dietary iron intake and bioavailability, as well as circulating levels of hepcidin, leptin and interleukin-6 (IL-6), in overweight vs normal weight children. Design: In 6-14-year-old normal and overweight children (n ¼ 121), we measured dietary iron intake, estimated iron bioavailability and determined body mass index s.d. scores (BMI-SDS). In all children (n ¼ 121), we measured fasting serum ferritin, soluble transferrin receptor (sTfR), C-reactive protein (CRP) and leptin; in a subsample, we measured IL-6 (n ¼ 68) and serum hepcidin (n ¼ 30). Results: There were no significant differences in dietary iron intake or bioavailability comparing normal and overweight children. The prevalence of iron-deficient erythropoiesis (an increased sTfR concentration) was significantly higher in the overweight than in the normal weight children (20 vs 6%, P ¼ 0.022, with sTfR concentrations of 4.40 ± 0.77 and 3.94 ± 0.88 mg l À1 , respectively, P ¼ 0.010). Serum hepcidin levels were significantly higher in the overweight children (P ¼ 0.001). BMI-SDS significantly correlated with sTfR (P ¼ 0.009), serum hepcidin (P ¼ 0.005) and the three measures of subclinical inflammation, namely CRP (Po0.001), IL-6 (Po0.001) and leptin (Po0.001). In a multiple regression model, serum hepcidin was correlated with BMI-SDS (P ¼ 0.020) and body iron (P ¼ 0.029), but not with the inflammatory markers. Conclusion: Our findings indicate that there is reduced iron availability for erythropoiesis in overweight children and that this is unlikely due to low dietary iron supply but rather due to hepcidin-mediated reduced iron absorption and/or increased iron sequestration.

Iron status in obese women

“…The presented study confirmed an inverse correlation between CRP and iron level, although the hepcidin level was not assessed. Similar to the results obtained by Yanoff, a positive correlation between C-reactive protein and BMI was found in the current study, confirming that obesity is associated with a low-grade inflammatory status that promotes release of acute-phase molecules [10,22].…”

“…The responsible mechanism is not fully understood, but it is believed that an increased level of pro-inflammatory cytokines, such as C-reactive protein, activates hepcidin expression, consecutively leading to restriction in intestinal iron absorption and macrophage iron release through hepcidin downregulating influence on ferroportin-1 [22]. It is thought that hepcidin inhibits expression of ferroportin 1, limiting iron absorption in duodenum, and iron ex-flux from cells to the plasma [23].…”

“…It is stated that increased body fat, especially visceral fat, predisposes towards worse iron homeostasis due to an increased rate of pro-inflammatory cytokines produced by visceral adipose tissue [20][21][22][23][24][25]. A large-scale study conducted on obese patients revealed also a positive correlation between TIBC and the percentage content of fat tissue.…”

Effect of body mass index reduction on serum hepcidin levels and iron status in obese children

“…These results support the data reported in some articles showing that obese patients have higher circulating hepcidin concentrations compared to normal weight subjects and corroborate the idea that the poor iron status frequently observed in obese children may be due to the hepcidin-mediated inhibition of dietary iron absorption. [6][7][8] Recently, in a group of obese women subjected to restrictive bariatric surgery, in agreement with our results, after weight loss, decreased serum hepcidin and improved functional iron status has been shown. 15 We also observed that change in hepcidin concentrations was associated with change in leptin independently of BMI.…”

“…4,5 Three recent studies have shown that, both in obese women and in obese children, serum hepcidin levels were significantly higher compared with normal weight controls and have focused on the hepcidin-mediated inhibition of dietary iron absorption in obese patients. [6][7][8] To gain insight into the link between obesity and hepcidin, we performed an intervention study in a group of obese children and evaluated if body mass index (BMI) decrease may reduce circulating hepcidin levels, increasing, therefore, iron absorption and improving iron status.…”