THE EVALUATION OF NEW GENERATION INFLAMMATORY MARKERS IN CHILDREN WITH MORBID OBESITY AND METABOLIC SYNDROME

Year 2020, Volume: 8 Issue: 3, 479 - 488, 20.12.2020

Metin Donma , Sevgi Dilan Erselcan Ahsen Yilmaz Savaş Güzel , Orkide Donma

https://doi.org/10.37696/nkmj.781963

Abstract

Objective: Technological advancements, unbalanced nutrition, sedentary life style, are important factors in obesity. Obesity-inflammation relation is being examined. In this study, the relationships among new generation inflammatory markers in children with normal body mass index (C) as well as obese (OB), morbid obese (MO) children and those with metabolic syndrome (MetS) were investigated.
Materials and Methods: A total of 172 children participated in the study. Group 1 comprised children with normal body-mass index (control group) (C). Obese (OB) children were in Group 2, MO children constituted Group 3 and Group 4 included MO children with MetS. The number of cases were 37, 34, 51 and 50 in groups 1, 2, 3 and 4, respectively. Anthropometric measurements were recorded. Serum spexin, adropin, adipolipin, fibroblast growth factor-21 and fetuin-A levels were determined. Statistical analyses were performed.
Results: Spexin and adipolin levels were significantly lower in obese groups than C group (p<0.05). Although adropin and FGF-21 levels did not differ significantly between groups, levels were lower in OB, MO, and MetS groups than C group. There were no significant differences among fetuin-A levels of the groups. Correlations between spexin and adipolin were the highest. These cytokines were negatively correlated with obesity parameters. The correlations between these cytokines were weakened from C group to MetS group.
Conclusion: Decreasing spexin and adipolin levels in accordance with increasing obesity degrees and weakening of the correlation between these cytokines in MO group compared to C group may be helpful during the further investigation of obesity.

Keywords

Adipolin, children, metabolic syndrome, obesity, spexin

Supporting Institution

Tekirdag Namik Kemal University Scientific Research Projects Coordination Unit

Project Number

Project No: NKUBAP.02.TU.20.233

Thanks

Acknowledgment This study was supported by Tekirdag Namik Kemal University Scientific Research Projects Coordination Unit. (Project No: NKUBAP.02.TU.20.233.

MORBİD OBEZ VE METABOLİK SENDROMLU ÇOCUKLARDA YENİ NESİL ENFLAMATUVAR BELİRTEÇLERİN DEĞERLENDİRİLMESİ

Abstract

Amaç: Teknolojideki gelişmeler, dengesiz beslenme, sedanter hayat tarzı gibi yaşam değişiklikleri obezitenin gelişmesi için önemli faktörlerdir. Enflamasyon-obezite ilişkisi güncel bir konu olarak halen incelenmektedir. Bu çalışmada obez (OB), morbid obez (MO), metabolik sendromlu morbid obez (MetS) çocuklar ile sağlıklı, normal vücut kitle indeksi (K) olan çocuklarda yeni nesil enflamatuar belirteçler arasındaki ilişkiler araştırılmıştır.
Materyal ve Metod: Toplam 172 çocuk çalışma kapsamına alındı. Normal vücut kitle indeksine sahip çocuklar birinci grubu (kontrol grubu) (K) oluşturdu. Grup 2’de OB, Grup 3’te MO, Grup 4’te MetS’lu (MetS) çocuklar yer aldı. Olgu sayıları Grup 1, 2, 3 ve 4 için sırasıyla 37, 34, 51 ve 50 olarak belirlendi. Antropometrik ölçümler alındı. Serum speksin, adropin, adipolin, fibroblast büyüme faktörü-21 ve fetuin-A düzeyleri ölçüldü. İstatistiksel analizler gerçekleştirildi.
Bulgular: Speksin ve adipolin düzeyleri obez gruplarda K grubuna göre anlamlı düzeyde düşük bulundu (p<0.05). Adropin ve FGF-21 değerlerinde gruplar arasında anlamlı bir fark bulunmamasına rağmen düzeylerin, K grubuna göre OB, MO and MetS gruplarında azalmış olduğu saptandı. Fetuin-A düzeylerinde gruplar arasında anlamlı bir farklılık bulunamadı. En yüksek korelasyonlar speksin ve adipolin düzeyleri arasında bulundu. Bu sitokinler obezite parametreleri ile negatif bir ilişki içindeydi. Aynı sitokinler arasındaki ilişki K grubundan MetS grubuna doğru zayıflamakta idi.
Sonuçlar: Artan obezite derecelerine paralel olarak speksin ve adipolin seviyelerindeki azalma ve bu iki parametre arasındaki korelasyonun K grubuna göre MO grupta zayıflaması, obezitenin ileri düzeyde araştırılmasında yardımcı olabileceği düşüncesini ortaya koymaktadır.

Keywords

Adipolin, çocuk, metabolik sendrom, obezite, speksin

Project Number

Project No: NKUBAP.02.TU.20.233

References

• 1. Rundle AG, Factor-Litvak P, Suglia SF, Susser ES, Kezios KL, Lovasi GS, et al. Tracking of obesity in childhood into adulthood: Effects on body mass index and fat mass index at age 50. Child Obes. 2020;16(3):226-33.
• 2. Zatterale F, Longo M, Naderi J, Raciti GA, Desiderio A, Miele C, et al. Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes. Front Physiol. 2020;10:1607.
• 3. Christian Flemming GM, Bussler S, Körner A, Kiess W. Definition and early diagnosis of metabolic syndrome in children. J Pediatr Endocrinol Metab. [published online ahead of print, 2020 Jun 22].
• 4. Hamjane N, Benyahya F, Nourouti NG, Mechita MB, Barakat A. Cardiovascular diseases and metabolic abnormalities associated with obesity: What is the role of inflammatory responses? A systematic review. Microvasc Res. 2020;131:104023.
• 5. Shaunak M, Byrne CD, Davis N, Afolabi P, Faust SN, Davies JH. Non-alcoholic fatty liver disease and childhood obesity. Arch Dis Child. 2020;archdischild-2019-318063. [published online ahead of print, 2020 May 14]
• 6. Weihe P, Spielmann J, Kielstein H, Henning-Klusmann J, Weihrauch-Blüher S. Childhood obesity and cancer risk in adulthood.Curr Obes Rep. [published online ahead of print, 2020 Jun 9]
• 7. Donma M, Donma O. Links between inflammation and insulin resistance in children with morbid obesity and metabolic syndrome. Int J Med Health Sci. 2019;13(5):219-22.
• 8. Donma M, Donma O. The valuable triad of adipokine indices to differentiate pediatric obesity from metabolic syndrome: Chemerin, progranulin, vaspin. Int J Med Health Sci. 2018;12(5):240-4.
• 9. Akyol M, Alacacıoğlu A, Demir L, Kucukzeybek Y, Yildiz Y, Gumus Z, et al. The alterations of serum FGF-21 levels, metabolic and body composition in early breast cancer patients receiving adjuvant endocrine therapy. Cancer Biomarkers. 2017; 18: 1-9.
• 10. Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, Chen Y, et al. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology. 2008;149(12): 6018–27.
• 11. Afrisham R, Paknejad M, Ilbeigi D, Sadegh-Nejadi S, Gorgani-Firuzjaee S, Vahidi M. Positive correlation between circulating fetuin A and severity of coronary artery disease in men [published online ahead of print, 2020 Jun 1]. Endocr Metab Immune Disord Drug Targets. 2020;10.2174/1871530320666200601164253.
• 12. Zhou Z, Sun M, Jin H, Chen H, Ju H. Fetuin A to adiponectin ratio is a sensitive indicator for evaluating metabolic syndrome in the elderly. Lipids Health Dis. 2020;19(1):61.
• 13. Behrooz M, Vaghef-Mehrabany E, Ostadrahimi A. Different spexin level in obese vs normal weight children and its relationship with obesity related risk factors. Nutr Metab Cardiovasc Dis. 2020;30(4):674-82.
• 14. Lv SY, Zhou YC, Zhang XM, Chen WD, Wang YD. Emerging roles of NPQ/spexin in physiology and pathology. Front Pharmacol. 2019;10:457.
• 15. Liu Y, Sun L, Zheng L, Su M, Liu H, Wei Y, et al. Spexin protects cardiomyocytes from hypoxia-induced metabolic and mitochondrial dysfunction. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(1):25-33.
• 16. Ogawa H, Ohashi K, Ito M, Shibata R, Kanemura N, Yuasa D, et al. Adipolin/CTRP12 protects against pathological vascular remodelling through suppression of smooth muscle cell growth and macrophage inflammatory response. Cardiovasc Res. 2020;116(1):237–49.
• 17. Alipoor E, Salmani M, Yaseri M, Kolahdouz-Mohammadi R, Esteghamati A, Hosseinzadeh-Attar MJ. Role of type 2 diabetes and hemodialysis in serum adipolin concentrations: A preliminary study. Hemodial Int. 2019;23(4):472-8.
• 18. Choi HN, Yim JE. Plasma adropin as a potential marker predicting obesity and obesity-associated cancer in Korean patients with type 2 diabetes mellitus. J Cancer Prev. 2018;23(4):191-6.
• 19. Jasaszwili M, Billert M, Strowski MZ, Nowak KW, Skrzypski M. Adropin as a fat-burning hormone with multiple functions-Review of a decade of research. Molecules. 2020;25(3):549.
• 20. Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008;8(6):468–81.
• 21. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, et al. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005;115(6):1627–35.
• 22. Song JB, Hao KG, Chen X, Zhang YH,Cheng ZL, Mao S, et al. Fibroblast growth factor 21 prolongs lifespan and improves stress tolerance in the silkworm, Bombyx mori. Ann Transl Med. 2020;8(5):220.
• 23. Wang X, Zhu L, Hu J, Guo R, Ye S, Liu F, et al. FGF21 Attenuated LPS-induced depressive-like behavior via inhibiting the inflammatory pathway. Front Pharmacol. 2020;11:154.
• 24. Sim YS, Kang MJ, Oh YJ, Baek JW, Yang S, Hwang IT. Fetuin A as an alternative marker for insulin resistance and cardiovascular risk in prepubertal children. J Atheroscler Thromb. 2017; 24(10):1031-8.
• 25. Šimják P, Cinkajzlová A, Anderlová K, Kloučková J, Kratochvílová H, Lacinová Z, et al. Changes in plasma concentrations and mRNA expression of hepatokines fetuin A, fetuin B and FGF21 in physiological pregnancy and gestational diabetes mellitus. Physiol Res. 2018;67(Suppl 3):S531-S42.
• 26. Liu S, Hu W, He Y, Li L, Liu H, Gao L, et al. Serum Fetuin-A levels are increased and associated with insulin resistance in women with polycystic ovary syndrome. BMC Endocr Disord. 2020;20(1):67.
• 27. World Health Organization (WHO). The WHO Child Growth Standarts. Available at: http:// www.who.int /childgrowth/en/. Accessed on June 10, 2016.
• 28. Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S,et al. The metabolic syndrome in children and adolescents-an IDF consensus report. Pediatr Diabetes. 2007;8(5):299-306.
• 29. Ying L, Li N, He Z, Zeng X, Nan Y, Chen J, et al. Fibroblast growth factor 21 ameliorates diabetes-induced endothelial dysfunction in mouse aorta via activation of the CaMKK2/AMPKα signaling pathway. Cell Death Dis. 2019;10(9):665.
• 30. Donma MM, Donma O. Promising link between selenium and peroxisome proliferator activated receptor gamma in the treatment protocols of obesity as well as depression. Med Hypotheses. 2016;89:79-83.
• 31. Donma O, Donma M. The cooperation among insulin, cortisol and thyroid hormones in morbid obese children and metabolic syndrome. Int J Med Health Sci. 2018;12(5):213-6.
• 32. Ix JH, Sharma K. Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J Am Soc Nephrol. 2010;21(3):406-12.
• 33. Allardyce CS: Fat Chemistry: The Science behind Obesity. Cambridge, UK: The Royal Society of Chemistry Publishing, 2015.
• 34. Yen M, Donma O, Yildizfer F, Ekmekci O, Karatas-Kul ZA, Imal AE, et al. Association of fetuin A, adiponectin, interleukin 10 and total antioxidant capacity with IVF outcomes. Iran J Reprod Med. 2014;12(11):747-54.
• 35. Liu P, Zhang X, Hu J, Cui L, Zhao S, Jiao X, et al. Dysregulated cytokine profile associated with biochemical premature ovarian insufficiency. Am J Reprod Immunol. 2020;e13292. [published online ahead of print, 2020 Jun 21]
• 36. Al-Daghri NM, Alenad A, Al-Hazmi H, Amer OE, Hussain SD, Alokail MS. Spexin levels are associated with metabolic syndrome components. Dis Markers. 2018;2018:1679690.
• 37. Al-Daghri NM, Wani K, Yakout SM, Al-Hazmi H, Amer OE, Hussain SD, et al. Favorable changes in fasting glucose in a 6-month self-monitored lifestyle modification programme inversely affects spexin levels in females with prediabetes. Sci Rep. 2019; 9(1):9454.
• 38. Gu L, Ma Y, Gu M, Zhang Y, Yan S, Li N, et al. Spexin peptide is expressed in human endocrine and epithelial tissues and reduced after glucose load in type 2 diabetes. Peptides. 2015; 71: 232–9.
• 39. Karaca A, Bakar-Ates F, Ersoz-Gulcelik N. Decreased spexin levels in patients with type 1 and type 2 diabetes. Med Princ Pract. 2018;27(6):549-54.
• 40. Kumar S, Hossain MJ, Javed A, Kullo IJ, Balagopal PB. Relationship of circulating spexin with markers of cardiovascular disease: a pilot study in adolescents with obesity. Pediatr Obes. 2018;13(6):374-80.
• 41. Fadaei R, Moradi N, Kazemi T, Chamani E, Azdaki N, Moezibady SA, et al. Decreased serum levels of CTRP12/adipolin in patients with coronary artery disease in relation to inflammatory cytokines and insulin resistance.Cytokine. 2019;113:326-31.
• 42. Kasabri V, Al-Ghareeb MI, Saleh MI, Suyagh M, Halaseh L, Al-Sarraf I, et al. Proportional correlates of adipolin and cathepsin S in metabolic syndrome patients with and without prediabetes. Diabetes Metab Syndr. 2019;13(4):2403-8.
• 43. Zang H, Jiang F, Cheng X, Xu H, Hu X. Serum adropin levels are decreased in Chinese type 2 diabetic patients and negatively correlated with body mass index. Endocr J. 2018;65(7):685-91.
• 44. Mansur AJ. Adropin and irisin in patients with cardiac cachexia. Short Editorial. Arq Bras Cardiol. 2018;111(1):48-9.
• 45. Kalkan AK, Cakmak HA, Erturk M, Kalkan KE, Uzun F, Tasbulak O, et al. Adropin and irisin in patients with cardiac cachexia. Arq Bras Cardiol. 2018;111(1):39-47.
• 46. Li JY, Wang N, Khoso MH, Shen CB, Guo MZ, Pang XX, et al. FGF-21 elevated IL-10 production to correct LPS-induced inflammation. Inflammation. 2018;41(3):751-9.
• 47. Gao RY, Hsu BG, Wu DA, Hou JS, Chen MC. Serum fibroblast growth factor 21 levels are positively associated with metabolic syndrome in patients with type 2 diabetes. Int J Endocrinol. 2019;2019:5163245.
• 48. Reinehr T, Karges B, Meissner T, Wiegand S, Fritsch M, Holl RW, et al. Fibroblast growth factor 21 and fetuin-A in obese adolescents with and without type 2 diabetes. J Clin Endocrinol Metab. 2015;100(8):3004-10.
• 49. González E, Díez JJ, Bajo MA, del Peso G, Grande C, Rodríguez O, et al. Fibroblast growth factor 21 (FGF-21) in peritoneal dialysis patients: Natural history and metabolic implications. PLoS One. 2016;11(3):e0151698.
• 50. Yilmaz A, Yilmaz T, Gunay M. Elevated serum fetuin-A levels are associated with grades of retinopathy in type 2 diabetic patients. Int Ophthalmol. 2018;38(6):2445-50.
• 51. Khadir A, Kavalakatt S, Madhu D, Hammad M, Devarajan S, Tuomilehto J, et al. Fetuin-A levels are increased in the adipose tissue of diabetic obese humans but not in circulation. Lipids Health Dis. 2018;17(1):291.
• 52. Hennige AM, Staiger H, Wicke C, Machicao F, Fritsche A, Häring H-U, et al. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One. 2008;3(3):e1765.