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.

The role of iron metabolism in chronic diseases related to obesity

“…In particular, obese patients with combined chronic inflammatory conditions are more susceptible to hypoferritinemia (serum ferritin deficiency), which can be considered to be related to iron deficiency caused by the inflammatory response (Yanoff et al 2007 ). Serum ferritin levels are positively correlated with serum insulin and HOMA-IR values (Moore Heslin et al 2021 ), and there is evidence of an association between serum iron levels and metabolic syndrome (Sachinidis et al 2020 ). Lowering plasma ferritin was proved to improve NAFLD in obese patients, suggesting that consideration of iron status is imperative in the treatment of obesity-related metabolic dysfunction (Moore Heslin et al 2021 ).…”

“…Serum ferritin levels are positively correlated with serum insulin and HOMA-IR values (Moore Heslin et al 2021 ), and there is evidence of an association between serum iron levels and metabolic syndrome (Sachinidis et al 2020 ). Lowering plasma ferritin was proved to improve NAFLD in obese patients, suggesting that consideration of iron status is imperative in the treatment of obesity-related metabolic dysfunction (Moore Heslin et al 2021 ). Here, we summarize the pathophysiological mechanisms of iron action in obesity and its related metabolic diseases to provide new perspectives for the prevention and treatment of obesity (Fig.…”

Correlations Between Iron Status and Body Composition in Patients With Type 2 Diabetes Mellitus

“…In contrast, lesser degrees of iron overload are required to raise TSAT levels. This in general makes increased TSAT a more sensitive marker than ferritin ( 40 ). Moreover, in the current article, we review the existing literature about the relationship between iron status and obesity without diabetes.…”

“…Moreover, in the current article, we review the existing literature about the relationship between iron status and obesity without diabetes. An analysis based on a subsample from the cross-sectional Irish National Adult Nutrition Survey (2008–2010) by Heslin et al has indicated that excessive body fat was significantly associated with increased serum hepcidin and ferritin and an increased prevalence of severe risk of iron overload ( 41 ). Hepcidin inhibits dietary absorption in the duodenum, the release of recycled iron from macrophages, and the exit of stored iron from hepatocytes by downregulation of ferroportin ( 42 ).…”

“…Lobo et al have found that liver iron accumulation occurred in the high-fat-diet-fed animals, and body adiposity was positively associated with liver iron stores but negatively associated with serum iron levels ( 48 ). Heslin et al have revealed that the disturbances in iron homeostasis observed in individuals with excess adiposity are likely due to the inflammation of adipose-derived cytokines ( 41 ). Those at severe risk of iron overload display an increased prevalence of adipose tissue dysfunction.…”