The relationship between FSTL-1 (follistatin-related protein 1), FAM19A5 (family with sequence similarity 19, member A5) and CTRP-6 (C1q/TNF-related protein 6) levels and metabolic parameters in overweight children

Fatmagül Can; Veysel N. Baş; Fatma E. Koçak; İlknur Elifoğlu

doi:10.1515/jpem-2025-0169

Article

The relationship between FSTL-1 (follistatin-related protein 1), FAM19A5 (family with sequence similarity 19, member A5) and CTRP-6 (C1q/TNF-related protein 6) levels and metabolic parameters in overweight children

Fatmagül Can , Veysel N. Baş , Fatma E. Koçak and İlknur Elifoğlu

Published/Copyright: November 10, 2025

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information Explore this Subject

From the journal Journal of Pediatric Endocrinology and Metabolism Volume 39 Issue 1

Abstract

Objectives

There has been a growing rate of obesity among children and adolescents in recent years. Understanding the molecular mechanisms is crucial for grasping the onset and progression. Adipose tissue is recognized for its role in endocrine functions, releasing adipokines that play a vital role in the metabolic disruptions linked to obesity. Given the involvement of adipokines such as FSTL-1 (follistatin related protein 1), FAM19A5 (family with sequence similarity to 19 member A5), and CTRP-6 (C1q/tumor necrosis factor related protein 6) in this condition, the primary goal of our study was to explore the connection between these adipokines, metabolic parameters, anthropometric data, and obesity.

Methods

Seventy-nine children aged 0–10 years with exogenous obesity and 88 healthy children were included in the study. Adipokine levels were measured using ELISA. The relationship between biochemical parameters and anthropometric data was also evaluated.

Results

CTRP6 was 6.11 (4.95–8.13) ng/mL in the obese group and 2.79 (1.73–4.58) ng/mL in the healthy control group (p<0.0001); FSLT1 was 157.7 (130.5–216.5) ng/mL in the obese group and 187.4 (151.8–289.6) ng/mL in the healthy control group (p=0.0003), FAM19A5 was 590.8 (476.4–703.9) ng/L in the obese group and 736.8 (491.8–1,719.0) ng/L in the healthy control group (p=0.0003).

Conclusions

CTRP6 levels were found to be higher in obese children than in the healthy control group, while FSLT1 and FAM19A5 levels were found to be lower. Changes in the levels of these adipokines may play important roles in obesity and related conditions.

Keywords: children; obesity; FSTL-1; CTRP-6; FAM19A5

Corresponding author: Fatmagül Can, Assistant Professor, Department of Medical Biochemistry, Faculty of Medicine, Kutahya Health and Science University, Evliya Celebi Campus, Tavsanli Road 10. km, 43100, Kutahya, Türkiye, E-mail: fggun@hotmail.com

Research ethics: Document Date and Number: 12.07.2023–95783 Our study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: Our study was financially supported by REPUBLIC OF TURKEY KUTAHYA HEALTH SCIENCES UNIVERSITY RECTORATE (Scientific Research Projects Coordination Unit) with project number of TSA-2023-148.
Data availability: The datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request.

References

1. Kumar, S, Kelly, AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. Mayo Clin Proc 2017;92:251–65. https://doi.org/10.1016/j.mayocp.2016.09.017.Search in Google Scholar PubMed

2. Strauss, RS, Bradley, LJ, Brolin, RE. Gastric bypass surgery in adolescents with morbid obesity. J Pediatr 2001;138:499–504. https://doi.org/10.1067/mpd.2001.113043.Search in Google Scholar PubMed

3. Sunnetci, SE, Hatipoglu, HU. Increased serum circulating asprosin levels in children with obesity. Pediatr Int 2020;62:467–76. https://doi.org/10.1111/ped.14176.Search in Google Scholar PubMed

4. Whitaker, RC, Wright, JA, Pepe, MS, Seidel, KD, Dietz, WH. Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 1997;337:869–73. https://doi.org/10.1056/nejm199709253371301.Search in Google Scholar PubMed

5. Juonala, M, Magnussen, CG, Berenson, GS, Venn, A, Burns, TL, Sabin, MA, et al.. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med 2011;365:1876–85. https://doi.org/10.1056/nejmoa1010112.Search in Google Scholar PubMed

6. Zengi, S, Zengi, O, Kirankaya, A, Kucuk, SH, Erdogan Kutanis, E, Yigit, O. Serum omentin-1 levels in obese children. J Pediatr Endocrinol Metab 2019;32:247–51. https://doi.org/10.1515/jpem-2018-0231.Search in Google Scholar PubMed

7. Jamurtas, AZ, Stavropoulos-Kalinoglou, A, Koutsias, S, Koutedakis, Y, Fatouros, I. Adiponectin, resistin, and visfatin in childhood obesity and exercise. Pediatr Exerc Sci 2015;27:454–62. https://doi.org/10.1123/pes.2014-0072.Search in Google Scholar PubMed

8. Barraco, GM, Luciano, R, Semeraro, M, Prieto-Hontoria, PL, Manco, M. Recently discovered adipokines and cardio-metabolic comorbidities in childhood obesity. Int J Mol Sci 2014;15:19760–76. https://doi.org/10.3390/ijms151119760.Search in Google Scholar PubMed PubMed Central

9. Waki, H, Tontonoz, P. Endocrine functions of adipose tissue. Annu Rev Pathol 2007;2:31–56. https://doi.org/10.1146/annurev.pathol.2.010506.091859.Search in Google Scholar PubMed

10. Fan, N, Sun, H, Wang, Y, Wang, Y, Zhang, L, Xia, Z, et al.. Follistatin-like 1: a potential mediator of inflammation in obesity. Mediators Inflamm 2013;2013:752519. https://doi.org/10.1155/2013/752519.Search in Google Scholar PubMed PubMed Central

11. Wesołek-Leszczyńska, A, Pastusiak, K, Bogdański, P, Szulińska, M. Can adipokine FAM19A5 be a biomarker of metabolic disorders? Diabetes Metab Syndr Obes 2023;16:1651–66. https://doi.org/10.2147/DMSO.S460226.Search in Google Scholar PubMed PubMed Central

12. Tilg, H, Moschen, AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 2006;6:772–83. https://doi.org/10.1038/nri1937.Search in Google Scholar PubMed

13. Ouchi, N, Parker, JL, Lugus, JJ, Walsh, K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011;11:85–97. https://doi.org/10.1038/nri2921.Search in Google Scholar PubMed PubMed Central

14. Cheng, JX, Yu, K. Newly discovered adipokines associated with the pathogenesis of obesity and type 2 diabetes. Diabetes Metab Syndr Obes 2022;15:2381–9. https://doi.org/10.2147/dmso.s376163.Search in Google Scholar

15. Miyamae, T, Marinov, AD, Sowders, D, Wilson, DC, Devlin, J, Boudreau, R, et al.. Follistatin-like protein-1 is a novel proinflammatory molecule. J Immunol 2006;177:4758–62. https://doi.org/10.4049/jimmunol.177.7.4758.Search in Google Scholar PubMed

16. Liu, S, Wang, L, Wang, W, Lin, J, Han, J, Sun, H, et al.. TSC-36/FRP inhibits vascular smooth muscle cell proliferation and migration. Exp Mol Pathol 2006;80:132–40. https://doi.org/10.1016/j.yexmp.2005.07.005.Search in Google Scholar PubMed

17. Ouchi, N, Oshima, Y, Ohashi, K, Higuchi, A, Ikegami, C, Izumiya, Y, et al.. Follistatin-like 1, a secreted muscle protein, promotes endothelial cell function and revascularization in ischemic tissue through a nitric-oxide synthase-dependent mechanism. J Biol Chem 2008;283:32802–11. https://doi.org/10.1074/jbc.m803440200.Search in Google Scholar PubMed PubMed Central

18. Chan, QKY, Ngan, HYS, Ip, PPC, Liu, VWS, Xue, WC, Cheung, ANY. Tumor suppressor effect of Follistatin-like 1 in ovarian and endometrial carcinogenesis – a differential expression and functional analysis. Carcinogenesis 2009;30:114–21. https://doi.org/10.1093/carcin/bgn215.Search in Google Scholar PubMed

19. Shibanuma, M, Mashimo, J, Mita, A, Kuroki, T, Nose, K. Cloning from a mouse osteoblastic cell line of a set of transforming-growth-factor-beta 1-regulated genes, one of which seems to encode a Follistatin-related polypeptide. Eur J Biochem 1993;217:13–19. https://doi.org/10.1111/j.1432-1033.1993.tb18212.x.Search in Google Scholar PubMed

20. Horak, M, Kuruczova, D, Zlamal, F, Tomandl, J, Bienertova-Vasku, J. Follistatin-like 1 is downregulated in morbidly and super obese Central-European population. Dis Markers 2018;2018:4140815. https://doi.org/10.1155/2018/4140815.Search in Google Scholar PubMed PubMed Central

21. Lehr, S, Hartwig, S, Lamers, D, Famulla, S, Müller, S, Hanisch, FG, et al.. Identification and validation of novel adipokines released from primary human adipocytes. Mol Cell Proteomics 2012;11:M111.010504. https://doi.org/10.1074/mcp.m111.010504.Search in Google Scholar

22. Lee, Y-B, Hwang, H-J, Kim, JA, Hwang, SY, Roh, E, Hong, S-H, et al.. Association of serum FAM19A5 with metabolic and vascular risk factors in human subjects with or without type 2 diabetes. Diabetes Vasc Dis Res 2019;16:530–8. https://doi.org/10.1177/1479164119860746.Search in Google Scholar PubMed

23. Xie, K, Liu, L, Yin, C, Li, M, Wang, L, Lv, W, et al.. Follistatin-like 1 and family with sequence similarity to 19 member A5 levels are decreased in obese children and associated with glucose metabolism. Ann Nutr Metab 2022;78:213–21. https://doi.org/10.1159/000524624.Search in Google Scholar PubMed

24. Lei, X, Seldin, MM, Little, HC, Choy, N, Klonisch, T, Wong, GW. C1q/TNF-related protein 6 (CTRP-6) links obesity to adipose tissue inflammation and insulin resistance. J Biol Chem 2017;292:14836–50. https://doi.org/10.1074/jbc.M116.766808.Search in Google Scholar PubMed PubMed Central

25. Ellulu, MS, Patimah, I, Khaza’ai, H, Rahmat, A, Abed, Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci 2017:851–63. https://doi.org/10.5114/aoms.2016.58928.Search in Google Scholar PubMed PubMed Central

26. Khanna, D, Khanna, S, Khanna, P, Kahar, P, Patel, BM. Obesity: a chronic low-grade inflammation and its markers. Cureus 2022;14:e22711. https://doi.org/10.7759/cureus.22711.Search in Google Scholar PubMed PubMed Central

27. Thomas, EL, Fitzpatrick, JA, Malik, SJ, Taylor-Robinson, SD, Bell, JD. Whole body fat: content and distribution. Prog Nucl Magn Reson Spectrosc 2013;73:56–80. https://doi.org/10.1016/j.pnmrs.2013.04.001.Search in Google Scholar PubMed

28. Wu, WJ, Mo, DL, Zhao, CZ, Zhao, C, Chen, YS, Pang, WJ, et al.. Knockdown of CTRP-6 inhibits adipogenesis via lipogenic marker genes and Erk1/2 signalling pathway. Cell Biol Int 2015;39:54–62. https://doi.org/10.1002/cbin.10422.Search in Google Scholar PubMed

29. Lee, W, Kim, MJ, Park, EJ, Choi, YJ, Park, SY. C1qTNF-related protein-6 mediates fatty acid oxidation via the activation of the AMP-activated protein kinase. FEBS Lett 2010;584:968–72. https://doi.org/10.1016/j.febslet.2010.01.040.Search in Google Scholar PubMed

30. Kim, MJ, Lee, W, Park, EJ, Park, SY. C1qTNF-related protein-6 increases the expression of interleukin-10 in macrophages. Mol Cells 2010;30:59–64. https://doi.org/10.1007/s10059-010-0088-x.Search in Google Scholar PubMed

31. Fan, RH, Zhu, XM, Sun, YW, Peng, HZ, Wu, HL, Gao, WJ. CTRP-6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts. Biochem Biophys Res Commun 2016;475:356–60. https://doi.org/10.1016/j.bbrc.2016.05.013.Search in Google Scholar PubMed

32. Skinner, AC, Skelton, JA. Prevalence and trends in obesity and severe obesity among children in the United States, 1999-2012. JAMA Pediatr 2014;168:561–6. https://doi.org/10.1001/jamapediatrics.2014.21.Search in Google Scholar PubMed

33. Phelps, NH, Singleton, RK, Zhou, B, Heap, RA, Mishra, A, Bennett, JE, et al.. Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population representative studies with 222 million children, adolescents, and adults. Lancet 2024;403:1027–50. https://doi.org/10.1016/S0140-6736(23)02750-2.Search in Google Scholar PubMed PubMed Central

34. Liu, L, Li, M, Qin, Y, Liu, L, Xiao, Y. Serum Follistatin like 1 in children with obesity and metabolic-associated fatty liver disease. BMC Endocr Disord 2024;24:165. https://doi.org/10.1186/s12902-024-01702-5.Search in Google Scholar PubMed PubMed Central

Received: 2025-03-26

Accepted: 2025-10-22

Published Online: 2025-11-10

Published in Print: 2026-01-23

You are currently not able to access this content.

Articles in the same Issue

https://doi.org/10.1515/jpem-2025-0169

Keywords for this article

children; obesity; FSTL-1; CTRP-6; FAM19A5