Spexin and Fetuin A in Morbid Obese Children

Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Spexin, expressed in the central nervous system, has attracted much interest in feeding behavior, obesity, diabetes, energy metabolism and cardiovascular functions. Fetuin A is known as the negative acute phase reactant synthesized in the liver. Eosinophils are early indicators of cardiometabolic complications. Patients with elevated platelet count, associated with hypercoagulable state in the body, are also more liable to cardiovascular diseases (CVDs). In this study, the aim is to examine the profiles of spexin and fetuin A concomitant with the course of variations detected in eosinophil as well as platelet counts in morbid obese children. 34 children with normal-body mass index (N-BMI) and 51 morbid obese (MO) children participated in the study. Written-informed consent forms were obtained prior to the study. Institutional ethics committee approved the study protocol. Age- and sex-adjusted BMI percentile tables prepared by World Health Organization were used to classify healthy and obese children. Mean age ± SEM of the children were 9.3 ± 0.6 years and 10.7 ± 0.5 years in N-BMI and MO groups, respectively. Anthropometric measurements of the children were taken. BMI values were calculated from weight and height values. Blood samples were obtained after an overnight fasting. Routine hematologic and biochemical tests were performed. Within this context, fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein-cholesterol (HDL-C) concentrations were measured. Homeostatic model assessment for insulin resistance (HOMA-IR) values were calculated. Spexin and fetuin A levels were determined by enzyme-linked immunosorbent assay. Data were evaluated from the statistical point of view. Statistically significant differences were found between groups in terms of BMI, fat mass index, INS, HOMA-IR and HDL-C. In MO group, all parameters increased as HDL-C decreased. Elevated concentrations in MO group were detected in eosinophils (p < 0.05) and platelets (p > 0.05). Fetuin A levels decreased in MO group (p > 0.05). However, decrease was statistically significant in spexin levels for this group (p < 0.05). In conclusion, these results have suggested that increases in eosinophils and platelets exhibit behavior as cardiovascular risk factors. Decreased fetuin A behaved as a risk factor suitable to increased risk for cardiovascular problems associated with the severity of obesity. Along with increased eosinophils, increased platelets and decreased fetuin A, decreased spexin was the parameter, which reflects best its possible participation in the early development of CVD risk in MO children.

Keywords: Cardiovascular diseases, eosinophils, fetuin A, pediatric morbid obesity, platelets, spexin.

References:

[1] S. Xu and Y. Xue, “Pediatric obesity: Causes, symptoms, prevention and treatment,” Exp. Ther. Med., vol. 11, pp. 15-20, Jan. 2016.
[2] A. Ladla, P. Tongkrajai, S. Srisaenpang, P. Siviroj, S. Yutthakasemsunt, S. Tiamkao, V. Chotmongkol and K. Sawanyawisuth, “Which diagnostic criteria of metabolic syndrome are predictors of cardiovascular diseases in elderly populations?,” J. Clin. Transl. Endocrinol., vol. 23, no. 100248, Mar. 2021.
[3] D. J. Rader and G. K. Hovingh, “HDL and cardiovascular disease,” Lancet., vol. 384, no. 9943, pp. 618-625, Aug. 2014.
[4] X. Chen, Y. Zhang, Q. Chen, Q. Li, Y. Li and W. Ling, “Lower plasma fetuin-A levels are associated with a higher mortality risk in patients with coronary artery disease,” Arterioscler. Thromb. Vasc. Biol., vol. 37, no. 11, pp. 2213-2219, Nov. 2017.
[5] M. K. Jensen, T. M. Bartz, K. J. Mukamal, L. Djoussé, J. R. Kizer, R. P. Tracy, S. J. Zieman, E. B. Rimm, D. S. Siscovick, M. Shlipak and J. H. Ix, “Fetuin-A, type 2 diabetes, and risk of cardiovascular disease in older adults: the cardiovascular health study,” Diabetes Care., vol. 36, no. 5, pp. 1222-1228, May 2013.
[6] G. A. Laughlin, K. M. Cummins, C. L. Wassel, L. B. Daniels and J. H. Ix, “The association of fetuin-A with cardiovascular disease mortality in older community-dwelling adults: the Rancho Bernardo study,” J. Am. Coll. Cardiol., vol. 59, no. 19, pp. 1688-1696, May 2012.
[7] S. Kumar, M. J. Hossain, A. Javed, I. J. Kullo and P. B. Balagopal, “Relationship of circulating spexin with markers of cardiovascular disease: a pilot study in adolescents with obesity,” Pediatr. Obes., vol. 13, no. 6, pp. 374-380, Jun. 2018.
[8] S-Y. Lv, Y-C. Zhou, X-M. Zhang, W-D. Chen and Y-D. Wang, “Emerging roles of NPQ/Spexin in physiology and pathology,” Front. Pharmacol., vol. 10, pp. 457, May 2019.
[9] L. Toll, T. V. Khroyan, K. Sonmez, A. Ozawa, I. Lindberg, J. P. McLaughlin, S. O. Eans, A. A. Shahien and D. R. Kapusta, “Peptides derived from the prohormone proNPQ/spexin are potent central modulators of cardiovascular and renal function and nociception,” FASEB J., vol. 26, no. 2, pp. 947–954, Feb. 2012.
[10] M. Keçebaş, S. Güllülü, S. Sağ, F. Beşli, E. Açikgöz, E. Sarandöl and A. Aydinlar, “Serum fetuin-A levels in patients with systolic heart failure,” Acta Cardiol., vol. 69, no. 4, pp. 399-405, Aug. 2014.
[11] A. Akyüz, “Association of Fetuin-A with Carotid Intima-Media Thickness and Vascular Diseases”, In: Patel V., Preedy V. (eds) Biomarkers in Cardiovascular Disease. Biomarkers in Disease: Methods, Discoveries and Applications, Springer, Dordrecht., 2016.
[12] M. Minas, P. Mystridou, P. Georgoulias, S. Pournaras, K. Kostikas and K. I. Gourgoulianis, “Fetuin-A is associated with disease severity and exacerbation frequency in patients with COPD,” COPD., vol. 10, no. 1, pp. 28-34, Feb. 2013.
[13] M. Keskin, C. Culha, N. E. Gulcelik, E. Ademoglu, A. Keskin, and Y. Aral, “Fetuin-A levels determine cardiovascular risk in young diabetic patients,” Biomed. Res. India., vol. 28, no. 15, pp. 6767-6772, 2017.
[14] A. Khadir, S. Kavalakatt, D. Madhu, S. Devarajan, J. Abubaker, F. Al-Mulla and A. Tiss, “Spexin as an indicator of beneficial effects of exercise in human obesity and diabetes,” Sci. Rep., vol. 10, no. 1, pp. 10635, Jun. 2020.
[15] S. Lv, Y. Zhou, Y. Feng, X. Zhang, X. Wang, Y. Yang and X Wang, “Peripheral spexin inhibited food intake in mice,” Int. J. Endocrinol., vol. 2020, no. 4913785, Aug 2020.
[16] K. Abd El-Fattah Abul-Fadle, N. El-Huda A. Mohammed, R. M. Al-Sayed, M. M. Abdul-Rahman and A. I. Farag, “Effect of spexin treatment on cardiometabolic changes in obese type 2 diabetic rats,” Al-Azhar Med. J., vol. 49, no. 2, pp.735-758, 2020.
[17] R. Kelishadi, M. Hashemipour, P. Ashtijou, P. Mirmoghtadaee, P. Poursafa, N. Khavarian, and S. Ghatrehsamani, “Association of cell blood counts and cardiometabolic risk factors among young obese children,” Saudi Med. J., vol. 31, no. 4, pp. 406-412, Apr. 2010.
[18] K. Sakai, S. Inoue, T. Matsuyama, M. Takei, H. Ota, T. Katagiri, and Y. Koboyashi, “Eosinophils may be involved in thrombus growth in acute coronary syndrome,” Int. Heart J., vol. 50, no. 3, pp. 267-277, May 2009.
[19] A. V. Finn, “Eosinophils: an overlooked player in acute myocardial infarction. Editorial,” Coron. Artery Dis., vol. 26, pp. 99-100, March 2015.
[20] F. L. Roufosse, “Eosinophils: How they contribute to endothelial damage and dysfunction,” Presse Med., vol. 42, pp. 503-507, Apr. 2013.
[21] A. Furman-Niedziejko, P. Rostoff, R. Rychlak, K. Golinska-Grzybala, M. Wilczynska-Golonka, M. Golonka, and J. Nessler, “Relationship between abdominal obesity, platelet blood count and mean platelet volume in patients with metabolic syndrome,” Folia Med. Cracov, vol. 54, no.2, pp. 55-64, 2014.
[22] O. Donma and M. Donma, "Eosinophils and platelets: Players of the game in morbid obese boys with metabolic syndrome," Int. J. Med. Health Sci., vol. 11, no. 5, pp. 257 – 260, May 2017.
[23] O. Donma and M. Donma, "The potential involvement of platelet indices in insulin resistance in morbid obese children," Int. J. Med. Health Sci., vol. 14, no. 3, pp. 85 – 88, Mar. 2020.
[24] World Health Organization (WHO). The WHO Child Growth Standards. Available at: http://www.who.int/childgrowth/en/ Accessed on June 10, 2016.
[25] M. M. Donma, S. D. Erselcan, A. Yilmaz, S. Guzel and O. Donma, “The evaluation of new generation inflammatory markers in children with morbid obesity and metabolic syndrome,” Nam. Kem. Med. J., vol. 8, no. 3, pp.479-488, Dec. 2020.
[26] S. A. Aroner, D. E. St-Jules, K. J. Mukamal, R. Katz, M. G. Shlipak, M. H. Criqui, B. Kestenbaum, D. S. Siscovick, I. H. de Boer, N. S. Jenny, M. J. Budoff, J. H. Ix and MK Jensen “Fetuin-A, glycemic status, and risk of cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis,” Atherosclerosis., vol. 248, pp. 224-229, May 2016.
[27] L. E. Laugsand, J. H. Ix, T. M. Bartz, L. Djousse, J. R. Kizer, R. P. Tracy, A. Dehghan, K. Rexrode, O. L. Lopez, E. B. Rimm, D. S. Siscovick, C. J. O'Donnell, A. Newman, K. J. Mukamal and M. K. Jensen, “Fetuin-A and risk of coronary heart disease: A Mendelian randomization analysis and a pooled analysis of AHSG genetic variants in 7 prospective studies,” Atherosclerosis., vol. 243, no. 1, pp. 44-52, Nov. 2015.
[28] K. Türkmen, H. Kayıkçıoğlu, O. Özbek, A. GaIpov, F. H. Yerlikaya, A. Toker and H. Z. Tonbul, “Relationship between fetuin-A, inflammation, coronary artery calcification in hemodialysis and peritoneal dialysis patients,” Turk. Neph. Dial. Transpl., vol. 21, no. 2, pp. 111-117, 2012.
[29] K. Mori, Y. Ikari, S. Jono, M. Emoto, A. Shioi, H. Koyama, T. Shoji, E. Ishimura, M. Inaba, K. Hara and Y. Nishizawa, “Fetuin-A is associated with calcified coronary artery disease,” Coron. Artery Dis., vol. 21, no. 5, pp. 281-285, Aug. 2010.
[30] M. Behrooz, E. Vaghef-Mehrabany and A. Ostadrahimi, “Different spexin level in obese vs normal weight children and its relationship with obesity related risk factors,” Nutr. Metab. Cardiovasc. Dis., vol. 30, no. 4, pp. 674-682, Apr. 2020.
[31] T. Chen, F. Wang, Z. Chu, L. Sun, H. Lv, W. Zhou, J. Shen, L. Chen and M. Hou, “Circulating spexin decreased and negatively correlated with systemic insulin sensitivity and pancreatic β cell function in obese children,” Ann. Nutr. Metab., vol. 74, no. 2, pp. 125-131, 2019.
[32] G. A. Ilhan, and B. Yildizhan, “Spexin as a new metabolic biomarker in women with polycystic ovary syndrome,” Fert. Ster., vol. 110, no. 4, e118, Sept. 2018.