Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 32451
Relationship between Hepatokines and Insulin Resistance in Childhood Obesity

Authors: Mustafa M. Donma, Orkide Donma


Childhood obesity is an important clinical problem, because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21) and fetuin A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21 and fetuin A in childhood obesity, to point out possible differences between the obesity groups and to investigate possible associations among these three hepatokines in obese and morbid obese children. A total of 132 children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean±SD values of ages. Body mass index values of the obese and morbid obese groups were 25.0±3.5 kg/m2 and 29.8±5.7 kg/m2, respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants and the Ethics Committee of the institution approved the study protocol. Blood samples were obtained after an overnight fasting. Routine biochemical tests including glucose- and lipid-related parameters were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study were performed by SPSS for Windows. Statistical difference was accepted significant when p < 0.05. Statistically significant differences were found for insulin, triglyceride, high density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbid obese group. Higher adropin and fetuin A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbid obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin A (r = 0.373, p = 0.001). In conclusion, increased levels observed in adropin, FGF-21 and fetuin A have shown that these hepatokines possess increasing potential going from the obese to morbid obese state. Out of the correlations found with IR index, the most affected hepatokine was fetuin A, the parameter possibly used as the indicator of the advanced obesity stage.

Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 383


[1] S. O. Jensen-Cody, and M. J. Potthoff, “Hepatokines and metabolism: Deciphering communication from the liver,” Mol. Metab., vol. 44, no. 101138, Feb. 2021.
[2] H. S. Han, G. Kang, J. S. Kim, B. H. Choi, and S. H. Koo, “Regulation of glucose metabolism from a liver-centric perspective,” Exp. Mol. Med., vol. 48, no. 3, pp. e218, 2016.
[3] Y. S. Sim, M. J. Kang, Y. J. Oh, J. W. Baek, S. Yang, and I. T. Hwang, “Fetuin A as an alternative marker for insulin resistance and cardiovascular risk in prepubertal children,” J. Atheroscler. Thromb., vol. 24, no. 10, pp. 1031-1038, 2017.
[4] E. S. Hong, C. Lim, H. Y. Choi, Y. K. Lee, E. J. Ku, J. H. Moon, K. S. Park, H. C. Jang, and S. H. Choi, “Plasma fibroblast growth factor 21 levels increase with ectopic fat accumulation and its receptor levels are decreased in the visceral fat of patients with type 2 diabetes,” BMJ Open Diab. Res. Care, vol.7, no. e000776, 2019.
[5] L. Berti, M. Irmler, M. Zdichavsky, T. Meile, A. Böhm, N. Stefan, A. Fritsche, J. Beckers, A. Königsrainer, H. U. Häring, M. H. de Angelis, and H. Staiger, “Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes,” Mol. Metab., vol.4, no.7, pp.519-527, May 2015.
[6] R. Y. Gao, B. G. Hsu, D. A. Wu, J. S. Hou, and M. C. Chen, “Serum fibroblast growth factor 21 levels are positively associated with metabolic syndrome in patients with type 2 diabetes,” Int. J. Endocrinol., vol. 2019, no. 5163245, Sep. 2019.
[7] L.D. BonDurant, and M. J. Potthoff, “Fibroblast growth factor 21: a versatile regulator of metabolic homeostasis,” Ann. Rev. Nutr., vol. 38, pp.173-196, 2018.
[8] G. Gaich, J. Y. Chien, H. Fu, L. C. Glass, M. A. Deeg, W. L. Holland, A. Kharitonenkov, T. Bumol, H. K. Schilske, and D. E. Moller, “The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes,” Cell Metab., vol.18, no.3, pp.333-340, Sep. 2013.
[9] J. Sonoda, M. Z. Chen, and A. Baruch, "FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases," Horm. Mol. Biol. Clin. Invest., vol. 30, no. 2, 2017.
[10] L. Geng, K. S. L. Lam, and A. Xu, “The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic,” Nat. Rev. Endocrinol., vol. 16, no. 11, pp. 654-667, Nov. 2020.
[11] A. Hosseini, M. Shanaki, S. Emamgholipour, M. Nakhjavani, F. Razi, and T. Golmohammadi, “Elevated serum levels of adropin in patients with type 2 diabetes mellitus and its association with insulin resistance,” J. Biol. Today's World., vol. 5, no. 3, pp.44-49, Mar. 2016.
[12] S. Zhang, Q. Chen, X. Lin, M. Chen, and Q. Liu, “A review of adropin as the medium of dialogue between energy regulation and immune regulation,” Oxid. Med. Cell Longev., vol. 2020, no. 3947806, Mar. 2020.
[13] H. Zang, F. Jiang, X. Cheng, H. Xu, and X. Hu, “Serum adropin levels are decreased in Chinese type 2 diabetic patients and negatively correlated with body mass index,” Endocr. J., vol. 65, no.7, pp.685-691, Jul. 2018.
[14] L. Herrero, O. de Dios, T. Gavela-Pérez, P. Riestra, A. Jois, L. Soriano-Guillén, and C. Garcés, “Opposite association of adropin concentrations with obesity in prepubertal children compared with adolescents,” Obesity (Silver Spring), vol. 28, no. 9, pp. 1736-1741, Sep. 2020.
[15] J. B. Chang, N. F. Chu, F. H. Lin, J. T. Hsu, and P. Y. Chen, “Relationship between plasma adropin levels and body composition and lipid characteristics amongst young adolescents in Taiwan,” Obes. Res. Clin. Pract., vol. 12, no. Suppl 2, pp.101-107, Jan-Feb 2018
[16] C. Kocaoglu, M. Buyukinan, S. S. Erdem, and A. Ozel, “Are obesity and metabolic syndrome associated with plasma adropin levels in children?,” J. Pediatr. Endocrinol. Metab., vol. 28, no. 11-12, pp. 1293-1297, Nov. 2015.
[17] R. Afrisham, M. Paknejad, D. Ilbeigi, S. Sadegh-Nejadi, S. Gorgani-Firuzjaee, and M. Vahidi, “Positive correlation between circulating fetuin-A and severity of coronary artery disease in men,” Endocr. Metab. Immune Disord. Drug Targets., vol. 21, no. 2, pp.338-344, 2021.
[18] World Health Organization (WHO). The WHO Child Growth Standards. Available at: Accessed on June 10, 2016.
[19] L. Bourebaba, and K. Marycz, “Pathophysiological implication of fetuin-A glycoprotein in the development of metabolic disorders: A concise review,” J. Clin. Med., vol. 8, no. 12, pp. 2033, Nov. 2019.
[20] S. Liu, W. Hu, Y. He, L. Li, H. Liu, L. Gao, G. Yang, and X. Liao, “Serum fetuin-A levels are increased and associated with insulin resistance in women with polycystic ovary syndrome,” BMC Endocr. Disord., vol. 20, no. 1, pp. 67, May 2020.
[21] M. Ghadimi, F. Foroughi, S. Hashemipour, M. R. Nooshabadi, M. H. Ahmadi, M. G. Yari, M. Kavianpour, and H. K. Haghighian, “Decreased insulin resistance in diabetic patients by influencing Sirtuin1 and Fetuin-A following supplementation with ellagic acid: a randomized controlled trial,” Diabetol. Metab. Syndr., vol. 13, no. 1, pp. 16, Feb. 2021.
[22] S. A. Willis, J. A. Sargeant, T. Yates, T. Takamura, H. Takayama, V. Gupta, E. Brittain, J. Crawford, S. A. Parry, A. E. Thackray, V. Varela-Mato, D. J. Stensel, R. M. Woods, C. J. Hulston, G. P. Aithal, and J. A. King, “Acute hyperenergetic, high-fat feeding increases circulating FGF21, LECT2, and fetuin-A in healthy men,” J. Nutr., vol. 150, no. 5, pp. 1076-1085, May 2020.
[23] 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