Fig. 7

Current understanding of links between obesity and iron deficiency. Obesity is marked by persistent systemic inflammation and increased production of pro-inflammatory cytokines and adipokines in adipose tissue. This directly impacts iron absorption from the duodenum enterocytes by inhibiting the iron transporter ferroportin 1, regulated by hepcidin. Moreover, pro-inflammatory cytokines like IL-6 act as powerful inducers of hepcidin in the liver, which may further impair iron absorption. Both, cytokines and hepcidin contribute to iron sequestration in macrophages, reducing iron recycling, sideremia, and iron availability for erythropoiesis. In obese conditions, compromised chest mobility during breathing causes restrictive ventilatory insufficiency which, along with potential episodes of sleep apnea, contribute to tissue hypoxia, another potential mechanism contributing to ID in obesity. These hypoxic conditions activate the hypoxia-inducible factor 1 pathway that induces the production of the hormone erythropoietin, primarily in the kidney, stimulating erythropoiesis in the bone marrow, leading to elevated circulating hemoglobin levels. This process demands a substantial amount of iron for hemoglobin synthesis, resulting in reduced availability. These combined factors result in an absolute and functional ID (mixed), reflected in low sideremia, TfSI and high sTfR as primary soluble biomarkers in serum. CRP, C-reactive protein; hypoxia-inducible factor 1, HIF-1; EPO, erythropoietin; TfSI, transferrin saturation index; sTfR, soluble transferrin receptor.