{"title":"Relationship between Iron-Related Parameters and Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis in Obese Children","authors":"Mustafa M. Donma, Orkide Donma, Savas Guzel","volume":187,"journal":"International Journal of Medical and Health Sciences","pagesStart":90,"pagesEnd":94,"ISSN":"1307-6892","URL":"https:\/\/publications.waset.org\/pdf\/10012596","abstract":"<p>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 \u00b1 34 mcrg\/dl and 75 \u00b1 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 \u00b1 19.1% vs. 26.7 \u00b1 14.6%, and 41 \u00b1 25 ng\/ml vs 44 \u00b1 26 ng\/ml. In N-BMI and OB groups, sTWEAK concentrations were measured as 351 ng\/L and 325 ng\/L, respectively (p &gt; 0.05). Correlation analysis revealed significant associations between sTWEAK levels and iron related parameters (p &lt; 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.<\/p>","references":"[1]\tR. De, K. U. Prakash, and E. S. Edison, \u201cComplex interactions in regulation of haematopoiesis-An unexplored iron mine,\u201d Genes (Basel), vol.12, no.8, pp.1270, Aug. 2021.\r\n[2]\tJ. L. Miller, \u201cIron deficiency anemia: a common and curable disease,\u201d Cold Spring Harb. Perspect. Med., vol.3, no.7, pp.a011866, Jul. 2013.\r\n[3]\tM. Ort\u00edz P\u00e9rez, M. A. V\u00e1zquez L\u00f3pez, M. Ib\u00e1\u00f1ez Alcalde, R. Galera Mart\u00ednez, M. Mart\u00edn Gonz\u00e1lez, F. Lend\u00ednez Molinos, and A. Bonillo Perales, \u201cRelationship between obesity and iron deficiency in healthy adolescents,\u201d Child. Obes., vol.16, no.6, pp.440-447, Sep. 2020. \r\n[4]\t\u00c1. Gonz\u00e1lez-Dom\u00ednguez, F. M. Visiedo-Garc\u00eda, J. Dom\u00ednguez-Riscart, R. Gonz\u00e1lez-Dom\u00ednguez, R. M. Mateos, and A. M. Lechuga-Sancho, \u201cIron metabolism in obesity and metabolic syndrome,\u201d Int. J. Mol. Sci., vol.21, no.15, pp.5529, Aug 2020. \r\n[5]\tA. C. Cepeda-Lopez, I. Aeberli, and M. B. Zimmermann, \u201cDoes obesity increase risk for iron deficiency? A review of the literature and the potential mechanisms,\u201d Int. J. Vitam. Nutr. Res., vol.80, no.4-5, pp.263-270, Oct. 2010.\r\n[6]\tD. Siyaram, P. Bhatia, D. Dayal, A. K. Bhalla, and R. Marathe, \u201cHypoferremic state in overweight and obese children,\u201d Indian Pediatr., vol.55, no.1, pp.72-73, Jan. 2018.\r\n[7]\tM. L. Muzzio, E. S. Lozano Chiappe, L. Kabakian, F. Ferraro, I. Land\u00f3, E. Alonso, J. Fern\u00e1ndez, S. Peredo, L. Brovarone, M. Pia Santucci, and T. Mero\u00f1o, \u201cEffects of pubertal status and inflammation on the use of ferritin to define iron deficiency in children with overweight or obesity,\u201d Nutr. Metab. Insights, vol.12, pp.1178638819839064, Apr.2019. \r\n[8]\tN. M. Alshwaiyat, A. Ahmad, W. M. R. Wan Hassan, and H. A. N. Al-Jamal, \u201cAssociation between obesity and iron deficiency (Review),\u201d Exp. Ther. Med., vol. 22, no.5, pp. 1268, Nov. 2021. \r\n[9]\tD. Pr\u00e1, S. I. Franke, J. A. Henriques, and M. Fenech, \u201cIron and genome stability: an update,\u201d Mutat. Res., vol.733, no.1-2, pp.92-99. May 2012. \r\n[10]\tE. Luporsi, A. Turpin, V. Massard, S. Morin, B. Chauffert, A. Carnot, P. Cacoub; Behalf of the CARENFER Study Group, \u201cIron deficiency in patients with cancer: a prospective cross-sectional study,\u201d BMJ Support. Palliat. Care, 2021 Jul 30:bmjspcare-2021-002913. Epub ahead of print. \r\n[11]\tZ. Levi, J. D. Kark, L H. Katz, G. Twig, E. Derazne, D. Tzur, Y. Leibovici Weissman, A. Leiba, I. Lipshiez, L. Keinan Boker, and A. Afek,\u201cAdolescent body mass index and risk of colon and rectal cancer in a cohort of 1.79 million Israeli men and women: A population-based study,\u201d Cancer, vol.123, pp. 204022-204030, Oct. 2017. \r\n[12]\tH. Scher\u00fcbl, \u201cExcess body weight and gastrointestinal cancer risk,\u201d Visc. Med., vol.37, no.4, pp.261-266, Aug. 2021. \r\n[13]\tX. Wang, Z. Guo, Z. Ding, and J. L. Mehta, \u201cInflammation, autophagy, and apoptosis after myocardial infarction,\u201d J. Am. Heart Assoc., vol.7, no.9, pp.e008024, 2018.\r\n[14]\tR. S. Y. Wong, \u201cApoptosis in cancer: from pathogenesis to treatment,\u201d J. Exp. Clin. Cancer Res., vol.30, no.1, pp.87, 2011. \r\n[15]\tE. O. Melin, J. Dereke, and M. Hillman, \u201cLow levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study,\u201d BMC Psychiatry, vol.20, no.1, pp.574, Dec. 2020. \r\n[16]\tA. D\u00edaz-L\u00f3pez, M. R. Chac\u00f3n, M. Bull\u00f3, E. Maym\u00f3-Masip, M. A. Mart\u00ednez-Gonz\u00e1lez, R. Estruch, J. Vendrell, J. Basora, J. D\u00edez-Espino, M-I. Covas, and J. Salas-Salvad\u00f3, \u201cSerum sTWEAK concentrations and risk of developing Type 2 diabetes in a high cardiovascular risk population: A nested case-control study,\u201d J. Clin. Endocrinol. Metab., vol. 98, no. 8, pp.3482-3490, Aug. 2013. \r\n[17]\tA. D\u00edaz-L\u00f3pez, M. Bull\u00f3, M. R. Chac\u00f3n, R. Estruch, J. Vendrell, J. D\u00edez-Espino, M. Fit\u00f3, D. Corella, and J. Salas-Salvad\u00f3, \u201cReduced circulating sTWEAK levels are associated with metabolic syndrome in elderly individuals at high cardiovascular risk,\u201d Cardiovasc. Diabetol., vol. 13, pp.51, Feb. 2014. \r\n[18]\tF. X. Avil\u00e9s-Jurado, X. Terra, D. G\u00f3mez, J. C. Flores, A. Ravent\u00f3s, E. Maym\u00f3-Masip, X. Le\u00f3n, V. Serrano-Gonzalvo, J. Vendrell, E. Figuerola, and M. R. Chac\u00f3n, \u201cLow blood levels of sTWEAK are related to locoregional failure in head and neck cancer,\u201d Eur. Arch. Otorhinolaryngol., vol.272, no.7, pp.1733-1741, Jul. 2015.\r\n[19]\tA. Altuna-Coy, X. Ruiz-Plazas, M. Alves-Santiago, J. Segarra-Tom\u00e1s, and M. R. Chac\u00f3n, \u201cSerum levels of the cytokine TWEAK are associated with metabolic status in patients with prostate cancer and modulate cancer cell lipid metabolism in vitro,\u201d Cancers (Basel), vol.13, no.18, pp.4688, Sep. 2021. \r\n[20]\tJ. M. G\u00f3mez-Martin, E. Aracil, M. Insenser, G. de la Pe\u00f1a, M. A. Lasunci\u00f3n, J. Galindo, H. F. Escobar-Morreale, J. A. Balsa, and J. I. Botella-Carretero, \u201cChanges in soluble TWEAK concentrations, but not those in amyloid-\u03b2(1-40), are associated with a decrease in carotid intima-media thickness after bariatric surgery in obese women,\u201d Obes. Facts, vol.13, no.3, pp.321-330, 2020. \r\n[21]\t\u00d6. Y\u0131ld\u0131r\u0131m, T. Demircan, \u00d6. T\u00fcfek\u00e7i, \u00d6. K\u0131z\u0131lca, P. Kuyum, M. K\u0131r, A. Abac\u0131, N. \u00dcnal, N. Arslan, E. B\u00f6ber, \u015e. Y\u0131lmaz, and H. \u00d6ren, \u201cAnemia and its effect on cardiovascular findings in obese adolescents,\u201d Turk. J. Haematol., vol.35, no.3, pp.192-196, Aug. 2018.\r\n[22]\tL. M. Blanco-Colio, J. L. Mart\u00edn-Ventura, B. Mu\u00f1\u00f3z-Garc\u00eda, J. Orbe, J. A. P\u00e1ramo, J. B. Michel, A. Ortiz, O. Meilhac, and J. Egido, \u201cIdentification of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) as a possible biomarker of subclinical atherosclerosis,\u201d Arterioscler. Thromb. Vasc. Biol., vol.27, no.4, pp.916-922, Apr. 2007. \r\n[23]\tWorld Health Organization (WHO). The WHO Child Growth Standards. 2016 June. Access: http:\/\/www.who.int\/childgrowth\/en\/ \r\n[24]\tO. Suteerojntrakool, T. Khongcharoensombat, S. Chomtho, C. Bongsebandhu-Phubhakdi, T. Tempark, and M. Fewtrell, \u201cAnthropometric markers and iron status of 6-12-year-old Thai children: Associations and predictors,\u201d J. Nutr. Metab., vol.2021, pp.9629718, Apr. 2021. \r\n[25]\tR. Bridges, \u201cIron metabolism and sideroblastic anemia,\u201d in Hematology of Infancy and Childhood, D.G. Nathan, F. A. Oski, Eds. Philadelphia, PA: W.B. Saunders Company, 1992, pp.391.\r\n[26]\tC. J. Thiele, M. Kastan, \u201cBiology of childhood cancer,\u201d in Principles and Practice of Pediatric Oncology, P. A. Pizzo, D. G. Poplack, Eds. Philadelphia, PA: Lippincott Williams & Wilkins, 2002, pp.89.\r\n[27]\tA. L. Fisher, D. N. Srole, N. J. Palaskas, D. Meriwether, S. T. Reddy, T. Ganz, and E. Nemeth, \u201cIron loading induces cholesterol synthesis and sensitizes endothelial cells to TNF\u03b1-mediated apoptosis,\u201d J. Biol. Chem., vol.297, no.4, pp.101156, Sep 2021. \r\n[28]\tY. Feng, P. Y. He, W. D. Kong, W. J. Cen, P. L. Wang, C. Liu, W. Zhang, S. S. Li, and J. W. Jiang, \u201cApoptosis-promoting properties of miR-3074-5p in MC3T3-E1 cells under iron overload conditions,\u201d Cell Mol. Biol. Lett.,vol. 26, no. 1, pp.37, Aug. 2021. \r\n[29]\tD. D. Im, C. H. Ho, and R. Y. Chan, \u201cHypersegmented neutrophils in an adolescent male with heatstroke,\u201d J. Pediatr. Hematol. Oncol., vol.37, pp.488, 2015. \r\n[30]\tS. G. Berrak, M. Angaji, E. Turkkan, C. Canpolat, C. Timur, and E. Eksioglu-Demiralp, \u201cThe effects of iron deficiency on neutrophil\/monocyte apoptosis in children,\u201d Cell Prolif., vol. 40, no.5, pp.741-754, Oct. 2007.","publisher":"World Academy of Science, Engineering and Technology","index":"Open Science Index 187, 2022"}