It is also much more reliable than serum ferritin levels, which may be increased far beyond the real amount of iron excess in several common conditions such as metabolic abnormalities,24 excessive alcohol consumption,25 inflammatory syndrome, or increased serum transaminases levels. In the present study there was no statistical linear correlation between AIR and BMI in either sex, but in women we found a

BMI threshold of 28 kg/m2 beyond which almost all AIR values remained lower than 6 g. Despite this, when compared selleck chemicals llc to women with BMI <28 kg/m2, women with BMI ≥28 kg/m2 were older, were more often postmenopausal, and did not have more pregnancies, all conditions associated with increased body iron stores. Moreover, when taking into account these potential confounding factors and others in a multivariate model, we found that BMI remained as an independent explanatory variable of AIR together with expected variables including parameters of iron metabolism, ALT, and hemoglobin. Laine et al.15 demonstrated

lower C282Y homozygosity expression, defined as TS <45%, in overweight women when compared to normal and lean women in a Britton general population. In a much larger sample, the present study confirms that both serum iron and transferrin saturation are significantly lower in women with BMI ≥28 than in women with BMI <28 kg/m2, which suggests a lower bioavailability of systemic iron in case of significant overweight, and then a lower rate find more of iron loading. Such data could support the role of an increased production of hepcidin in lowering iron burden in overweight C282Y women. Indeed, metabolic syndrome is associated with a minimal chronic inflammatory state related to the synthesis of proinflammatory cytokines and adipokines,26 in particular interleukin (IL)-627 and leptin.28 These cytokines

are known to promote hepcidin gene transcription through the STAT3 pathway.29 Moreover, several studies have shown that there is an overexpression of hepcidin in obesity. Bekri et al.16 medchemexpress reported that subcutaneous and visceral adipose hepcidin messenger RNA (mRNA) expression was significantly higher in obese compared to lean women, while liver mRNA expression was similar. Tussing-Humphreys et al.30 confirmed this result in obese women, but reported that hepatic hepcidin mRNA expression was strongly correlated with serum hepcidin, but not adipose hepcidin mRNA.16, 30 In a small sample of patients, a study reported that there was no oversecretion of hepcidin by subcutaneous adipose tissue whether the patient was obese or lean.31 Thus, the relationship that we found between serum hepcidin level and BMI in C282Y homozygous women suggests that the overproduction of hepcidin could be responsible for lower disease penetrance in the overweight cases. However, the mechanism of such an overproduction remains unclear, especially with respect to the tissular origin of hepcidin.