Obesity as an emerging risk factor for iron deficiency

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.

Figure 1

Summary of potential stimuli and characteristics which may affect the manifestation of the iron phenotype in obesity. Both iron deficiency and the dysmetabolic iron overload syndrome represent well-studied manifestations of disordered iron homeostasis. The net balance of underlying, frequently competing stimuli will likely define the iron phenotype in an individual patient.

Figure 2

Current understanding of molecular links between obesity and iron deficiency. Obese adipose tissue is characterized by an increased production of several pro-inflammatory cytokines and adipokines as opposed to healthy lean adipose tissue. These may directly impact iron absorption from the enterocyte. Additionally, pro-inflammatory cytokines such as interleukin-1 and -6 represent potent inducers of hepcidin production in the liver, which may further impair iron absorption. Both cytokines and hepcidin lead to iron retention in spleen, liver or bone marrow macrophages, thereby lowering serum iron concentrations and iron availability for erythropoiesis.