Abstract
Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS) or nonalcoholic fatty liver disease (NAFLD). This constellation has been named the “dysmetabolic iron overload syndrome (DIOS)”. Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN) along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity.
Highlights
Both iron deficiency (ID) and obesity are global epidemics affecting billions with regional disparities [1].It has become clear that iron deficiency and obesity do not merely represent the coincidence of two frequent conditions but are molecularly linked and mutually affect each other [2]
This review is mainly focused on iron deficiency (ID) in obesity and aspects of dysmetabolic iron overload syndrome (DIOS) are only mentioned where relevant to the main topic
The liver, which is the key regulator of iron homeostasis, in obesity and insulin resistance (IR) is characterized by lipid accumulation called nonalcoholic fatty liver disease (NAFLD)
Summary
Both iron deficiency (ID) and obesity are global epidemics affecting billions with regional disparities [1]. It has become clear that iron deficiency and obesity do not merely represent the coincidence of two frequent conditions but are molecularly linked and mutually affect each other [2]. A condition termed “dysmetabolic iron overload syndrome (DIOS)” has become the most frequent differential diagnosis for elevated ferritin concentrations, affecting approximately one-third of subjects with nonalcoholic fatty liver disease (NAFLD) or metabolic syndrome (MetS). DIOS is characterized by increased serum ferritin concentrations with normal or mildly elevated transferrin saturation in subjects with various components of MetS or NAFLD. True iron overload is rarely found in liver biopsy, and liver iron only weakly correlates with serum ferritin concentrations. It is associated with more severe manifestations and outcomes. Details of the clinical relevance and mechanisms of DIOS have been reviewed elsewhere [2,6]
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