Reduced serum iron levels are associated with metabolic dysfunction and sex-specific characteristics

Metabolic syndrome (MetS) is a clinical condition defined by abdominal obesity, insulin resistance, hypertension, and dyslipidaemia, associated with increased cardiovascular risk and type 2 diabetes (T2D). Emerging evidence suggests a role for iron metabolism and ferroptosis in the pathophysiology of MetS and its related complications. This study aimed to explore the association between serum iron levels and clinical, anthropometric, and biochemical parameters in a population with cardiometabolic risk factors. Weongoing treatment for such analysed data from 893 patients attending the Metabolic Disease Unit of the Interdisciplinary Medicine Department at the University of Bari "Aldo Moro". Patients with MetS, elevated BMI, hypertension, and T2D exhibited significantly lower serum iron levels compared to healthy controls. Serum iron showed a strong inverse correlation with age (r = - 0.09, p = 0.0061), fasting plasma glucose (r = - 0.10, p =  = .002), and HbA1c (r = - 0.18, p < 0.0001) in the overall population, while no correlations were found with Framingham Risk Score, triglycerides, waist circumference, and BMI. Conversely, when stratifying by sex, we observed that serum iron was inversely correlated with BMI (r = - 0.12, p = 0.008) and waist circumference (r = - 0.12, p = 0.008) in females only. Metabolic dysfunction is associated with reduced serum iron levels, with sex-specific patterns observed in relation to adiposity markers. Elucidating the interplay between iron metabolism, sex hormones, and adipose tissue biology may uncover new targets for personalized treatment strategies for metabolic diseases. Further research is warranted to clarify how modulation of iron homeostasis affects adipose tissue function, particularly in women with obesity and related metabolic disorders.