Relationship between Iron-Related Parameters and Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis in Obese Children

Iron is physiologically essential. However, it also participates in the catalysis of free radical formation reactions. Its deficiency is associated with amplified health risks. This trace element establishes some links with another physiological process related to cell death, apoptosis. Both iron deficiency and iron overload are closely associated with apoptosis. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has the ability to trigger apoptosis and plays a dual role in the physiological versus pathological inflammatory responses of tissues. The aim of this study was to investigate the status of these parameters as well as the associations among them in children with obesity, a low-grade inflammatory state. The study was performed on groups of children with normal body mass index (N-BMI) and obesity. 43 children were included in each group. Based upon age- and sex-adjusted BMI percentile tables prepared by the World Health Organization, children whose values varied between 85 and 15 were included in N-BMI group. Children, whose BMI percentile values were between 99 and 95, comprised obese (OB) group. Institutional ethical committee approval and informed consent forms were taken prior to the study. Anthropometric measurements (weight, height, waist circumference, hip circumference, head circumference, neck circumference) and blood pressure values (systolic blood pressure and diastolic blood pressure) were recorded. Routine biochemical analyses, including serum iron, total iron binding capacity (TIBC), transferrin saturation percent (Tf Sat %) and ferritin, were performed. sTWEAK levels were determined by enzyme-linked immunosorbent assay. study data were evaluated using appropriate statistical tests performed by the statistical program SPSS. Serum iron levels were 91 ± 34 mcrg/dl and 75 ± 31 mcrg/dl in N-BMI and OB children, respectively. The corresponding values for TIBC, Tf Sat %, ferritin were 265 mcrg/dl vs. 299 mcrg/dl, 37.2 ± 19.1% vs. 26.7 ± 14.6%, and 41 ± 25 ng/ml vs 44 ± 26 ng/ml. In N-BMI and OB groups, sTWEAK concentrations were measured as 351 ng/L and 325 ng/L, respectively (p > 0.05). Correlation analysis revealed significant associations between sTWEAK levels and iron related parameters (p < 0.05) except ferritin. In conclusion, iron contributes to apoptosis. Children with iron deficiency have decreased apoptosis rate in comparison with that of healthy children. sTWEAK is an inducer of apoptosis. OB children had lower levels of both iron and sTWEAK. Low levels of sTWEAK are associated with several types of cancers and poor survival. Although iron deficiency state was not observed in this study, the correlations detected between decreased sTWEAK and decreased iron as well as Tf Sat % values were valuable findings, which point out decreased apoptosis. This may induce a proinflammatory state, potentially leading to malignancies in the future lives of OB children.

Hematologic Inflammatory Markers and Inflammation-Related Hepatokines in Pediatric Obesity

Obesity in children particularly draws attention, because it may threaten the individual’s future life due to many chronic diseases it may lead to. Most of these diseases including obesity itself altogether are related to inflammation. For this reason, inflammation-related parameters gain importance. Within this context, complete blood cell counts, ratios or indices derived from these counts have recently found some platform to be used as inflammatory markers. So far, mostly adipokines were investigated within the field of obesity. Metabolic inflammation is closely associated with cellular dysfunction. In this study, hematologic inflammatory markers and cytokines produced predominantly by the liver (fibroblast growth factor-21 (FGF-21) and fetuin A) were investigated in pediatric obesity. Two groups were constituted from 76 obese children based on World Health Organization criteria. Group 1 was composed of children, whose age- and sex-adjusted body mass index (BMI) percentiles were between 95 and 99. Group 2 consists of children, who are above 99th percentile. The first and the latter groups were defined as obese (OB) and morbid obese (MO). Anthropometric measurements of the children were performed. Informed consent forms and the approval of the institutional ethics committee were obtained. Blood cell counts and ratios were determined by automated hematology analyzer. The related ratios and indexes were calculated. Statistical evaluation of the data was performed by SPSS program. There was no statistically significant difference in terms of neutrophil-to lymphocyte ratio, monocyte-to-high density lipoprotein cholesterol ratio and platelet-to-lymphocyte ratio between the groups. Mean platelet volume and platelet distribution width values were decreased (p < 0.05), total platelet count, red cell distribution width (RDW) and systemic immune inflammation index values were increased (p < 0.01) in MO group. Both hepatokines were increased in the same group, however increases were not statistically significant. In this group, also a strong correlation was calculated between FGF-21 and RDW when controlled by age, hematocrit, iron and ferritin (r = 0.425; p < 0.01). In conclusion, the association between RDW, a hematologic inflammatory marker, and FGF-21, an inflammation-related hepatokine, found in MO group is an important finding discriminating between OB and MO children. This association is even more powerful when controlled by age and iron-related parameters.