The content of adipokines and myokines in the blood of children and adolescents with different genotypes according to the polymorphism rs662 of the paraoxonase-1 gene

BACKGROUND. Among the many causes of obesity, genetic factors occupy a special place. An obvious role among them belongs to the genetic polymorphism of lipid metabolism enzymes, including paraoxonase-1 (PON-1). Until now, the character of the relationship between PON-1 polymorphism and the state of the endocrine function of mesenchymal tissues remains unclear. Its study will clarify the subtle mechanisms of the development of obesity in childhood and adolescence.

AIM. The aim of the study was to investigate the relationship between PON-1 polymorphism (rs662) and changes in the content of adipokines, myokines, and blood lipid metabolism in children and adolescents of different sexes with obesity.

MATERIALS AND METHODS. In 100 healthy children and adolescents of different sexes and 89 of their peers with obesity, a genetic study was conducted to assess the single nucleotide polymorphism of the PAO-1 (rs662) genes. In blood serum, total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol, triacylglycerols, glucose and aminotransferase activity (alanine aminotransferase and aspartate aminotransferase) were determined by photometric methods, as well as leptin, adiponectin, resistin, apelin, irisin, adipsin, myostatin, FGF21, osteocrine, oncostatin and insulin — by multiplex ELISA, and asprosin — by ELISA ones.

RESULTS. The patients with the homozygous Arg192/Arg allele, the development of complications of obesity in boys is limited and their occurrence in girls is prevented. In other variants of PON-1 polymorphism (Gln192/Gln and Gln192/Arg genotypes), protective mechanisms are formed in the body of girls aimed at preventing complications in obesity. In boys with the Gln192/Gln genotype, obesity reveals more pronounced shifts in lipid metabolism, manifestations of alteration and an increase in the mass of adipose tissue, and in boys-carriers of the heterozygous Gln192/Arg allele, atherogenesis processes increase.

CONCLUSION. Polymorphism of the paraoxonase-1 gene (rs662) contributes to the appearance of gender differences in changes in the content of adipokines and myokines in the blood during obesity in childhood and adolescence.

1. Di Cesare M, Sorić M, Bovet P, et al. The epidemiological burden of obesity in childhood: a worldwide epidemic requiring urgent action. BMC Med. 2019; 17(1):212. doi: https://doi.org/10.1186/s12916-019-1449-8

2. Le S, Törmäkangas T, Wang X, et al. Bidirectional associations between adiposity and physical activity: a longitudinal study from pre-puberty to early adulthood. Front Endocrinol (Lausanne). 2023; 14(12):6368-6379. doi: https://doi.org/10.3389/fendo.2023.1135852

3. Weihrauch-Blüher S, Schwarz P, Klusmann J-H. Childhood obesity: increased risk for cardiometabolic disease and cancer in adulthood. Metabolism. 2019; (92):147-152. doi: https://doi.org/10.1016/j.metabol.2018.12.001

4. Chai LK, Farletti R, Fathi L, Littlewood R. A rapid review of the impact of family-based digital interventions for obesity prevention and treatment on obesity-related outcomes in primary school-aged children. Nutrients. 2022; 14(22):4837. doi: https://doi.org/10.3390/nu14224837

5. Adiyeva M, Aukenov N, Nurzhanova A et al. The effect of AGTR1, AGТ, LPL, ADRB2 gene polymorphisms on central obesity in adolescents of the Kazakh population. Bratisl Lek Listy. 2023; 124(1):53-58. doi: https://doi.org/10.4149/BLL_2023_008

6. Kulaeva ED, Volchik VV, Bocharova OV, et al. Association of SNPs in lipid metabolism gene single nucleotide polymorphism with the risk of obesity in children. Genet Test Mol Biomarkers. 2021; 25(6):419-425. doi: https://doi.org/10.1089/gtmb.2020.0343

7. Chermon D, Birk R. Drinking habits and physical activity interact and attenuate obesity predisposition of TMEM18 polymorphisms carriers. Nutrients. 2023; 15(2):266. doi: https://doi.org/10.3390/nu15020266

8. Al-Serri A, Al-Bustan S, Al-Sabah SK, et al. Association between the lipoprotein lipase rs1534649 gene polymorphism in intron one with Body Mass Index and High Density Lipoprotein-Cholesterol. Saudi J Biol Sci. 2021; 28(8):4717-4722. doi: https://doi.org/10.1016/j.sjbs.2021.04.085.

9. Wang Wei, Tian Hu, Huilong Luo, et al. The cross-sectional study of hepatic lipase SNPs and plasma lipid levels. Food Sci Nutr. 2020; 8(2):1162-1172. doi: https://doi.org/10.1002/fsn3.1403

10. Tisato V, Romani A, Tavanti E. et al. Crosstalk between adipokines and paraoxonase 1: A new potential axis linking oxidative stress and inflammation. Antioxidants (Basel). 2019; 8(8):287. doi: https://doi.org/10.3390/antiox8080287

11. Fülöp P, Harangi M, Seres I, Paragh G. Paraoxonase-1 and adipokines: Potential links between obesity and atherosclerosis. Chem Biol Interact. 2016; 259(PtB):388-393. doi: https://doi.org/10.1016/j.cbi.2016.04.003

12. Levy D, Reichert CO, Bydlowski SP. Paraoxonases activities and polymorphisms in elderly and old-age diseases: An overview. Antioxidants. 2019; 8(5):118. doi: https://doi.org/10.3390/antiox8050118

13. Borovkova EI, Antipova NV, Komeenko TV, et al. Paraoxonase: The universal factor of antioxidant defense in human body. Vestn Ross Akad Med Nauk. 2017; 72(1):5-10. (In Russ.). doi: https://doi.org/10.15690/vramn764

14. Louis B, Nail V, Nachar O, et al. Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis. Angiogenesis. 2023; 26(3):463-475. doi: https://doi.org/10.1007/s10456-023-09875-8

15. Zhang Y, Jiang W, Sun W, et al. Neuroprotective roles of Apelin-13 in neurological diseases. Neurochem Res. 2023; 48(6):1648-1662. doi: https://doi.org/10.1007/s11064-023-03869-0

16. Choe SS, Huh JY, Hwang IJ, et al. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. Front Endocrinol (Lausanne). 2016; (7):30-37. doi: https://doi.org/10.3389/fendo.2016.00030

17. Shestopalov AV, Davydov VV, Tumanyan GT, et al. The gender factor effect for the edocryne function of mesenchymal tissues in children and adolescent. Molekulyarnaya meditsina. 2023; 21(2):52-59. (In Russ.). doi: https://doi.org/10.29296/24999490-2023-02-08

18. Pereira S, Cline DL, Glavas MM. et al. Tissue-specific effects of leptin on glucose and lipid metabolism. Endocr Rev. 2021; 42(1):1-28. doi: https://doi.org/10.1210/endrev/bnaa027

19. Vasyukova OV, Kasyanova YuV, Okorokov PL, Bezlepkina OB. Myokines and adipomyokines: inflammatory mediators or unique molecules of targeted therapy for obesity? Problems of Endocrinology. 2021; 67(4):36-45. (In Russ.). doi: https://doi.org/10.14341/probl12779.

20. Ahmed TM, Nassar M, Mohamed HAA, et al. Evaluation of serum levels of Irisin as a marker of endothelial dysfunction in patients with type 2 diabetes mellitus. Endocrinol Diabetes Metab. 2023; 6(3):e403. doi: https://doi.org/10.1002/edm2.403

21. Shen S, Liao Q, Chen X et al. The role of irisin in metabolic flexibility: Beyond adipose tissue browning. Drug Discov Today. 2022; 27(8):2261-2267. doi: https://doi.org/10.1016/j.drudis.2022.03.019.

22. Kasyanova YuV, Vasyukova OV, Okorokov PL, et al. Myokines in obese adolescents with aerobic exercise. Problems of Endocrinology. 2022; 68(4):102-110. (In Russ.). doi: https://doi.org/10.14341/probl13138

23. Li C, Cheng H, Adhikari BK et al. The Role of Apelin-APJ System in Diabetes and Obesity. Front Endocrinol (Lausanne). 2022; (13):820002. doi: https://doi.org/10.3389/fendo.2022.820002.

24. Dolgikh YuA, Verbovoy AF. Apelin: biological and pathophysiological effects. Pharmateka. 2018; (11):34-38. (In Russ.). doi: https://doi.org/10.18565/pharmateca.2018.11.34-38

25. Seres I, Bajnok L, Harangi M et al. Alteration of PON1 activity in adult and childhood obesity and its relation to adipokine levels. Adv Exp Med Biol. 2010; (660):129-142. doi: https://doi.org/10.1007/978-1-60761-350-3_12