MicroRNA-29a and microRNA-122 expressions and other inflammatory markers among obese children with diabetes

Nervana M.K. Bayoumy; Mohamed M. El-Shabrawi; Wafaa Elsayed; Hagar A. Kamal; Asmaa K. abdelmaogood; Shymaa Ahmed-Maher; Hamdy H. Omar; Ahmed Abdel-Rahman

doi:10.1515/jpem-2023-0320

Article

MicroRNA-29a and microRNA-122 expressions and other inflammatory markers among obese children with diabetes

Nervana M.K. Bayoumy , Mohamed M. El-Shabrawi , Wafaa Elsayed , Hagar A. Kamal , Asmaa K. abdelmaogood , Shymaa Ahmed-Maher , Hamdy H. Omar and Ahmed Abdel-Rahman

Published/Copyright: November 16, 2023

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 1

Abstract

Objectives

This study was conducted to study the expression of both microRNA-29a and microRNA-122, and serum levels of sestrin-2, interleukin-6 (IL-6), and other inflammatory markers among obese children with/and without diabetes mellitus.

Methods

One hundred obese children with diabetes in addition to 100 age- and sex-matched obese children without diabetes, and 100 age- and sex-matched apparently healthy children were included in the study. Expressions of both microRNA-29a and microRNA-122, and serum levels of sestrin-2, IL-6, tumor necrosis factor-α (TNF-α), and high sensitive-CRP (hsCRP) were measured for all included study populations.

Results

Study results showed that the expressions of both microRNA-29a and microRNA-122, serum levels of IL-6, TNF-α, and hsCRP were significantly higher among obese children with diabetes in comparison to both obese children without diabetes and healthy children. In contrast, serum sestrin level was significantly low among obese children with diabetes in comparison to the other study populations. Expressions of both microRNA-29a and microRNA-122 were correlated with waist circumference, BMI, total cholesterol, triglycerides, LDL-cholesterol, HbA_1c, c-peptide, glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), IL-6, hsCRP, and TNF-α among obese children with diabetes. However, serum sestrin-2 level was correlated inversely with these parameters. Higher expressions of both microRNA-29a and microRNA-122 among obese children either with or without diabetes mellitus (DM) can suggest their roles in the development of obesity among children.

Conclusions

The study results can hypothesize that down-regulation of these micro-RNAs may solve this health problem with its sequelae, a hypothesis that needs more studies.

Keywords: obesity; diabetes; inflammation

Corresponding author: Hamdy H. Omar, Internal Medicine Department, Faculty of Medicine, Suez Canal University, Egypt, E-mail: drhamdyomar@yahoo.com

Research ethics: The study was approved by the Ethics Committee of the Suez Canal University and carried out in accordance with the Helsinki Declaration.
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.
Data availability: The raw data can be obtained on request from the corresponding author.

References

1. Abarca-Gómez, L, Abdeen, ZA, Hamid, ZA, Abu-Rmeileh, NM, Acosta-Cazares, B, Acuin, C, et al.. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2,416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 2017;390:2627–42. https://doi.org/10.1016/s0140-6736(17)32129-3.Search in Google Scholar

2. Cui, X, Wang, P, Wei, Z. Emergency use of COVID-19 vaccines recommended by the World Health Organization (WHO) as of June 2021. Drug Discov Ther 2021;15:222–4. https://doi.org/10.5582/ddt.2021.01064.Search in Google Scholar PubMed

3. Salem, ME, Mahrous, OAF, El Shazly, HM, Kasemy, ZAA, Mehesin, SA-W. Epidemiology of obesity among primary school children (6–12 years), Menoufia Governorate. Menoufia Med J 2016;29:1000.Search in Google Scholar

4. Taghizadeh, S, Farhangi, MA. The effectiveness of pediatric obesity prevention policies: a comprehensive systematic review and dose–response meta-analysis of controlled clinical trials. J Transl Med 2020;18:1–21. https://doi.org/10.1186/s12967-020-02640-1.Search in Google Scholar PubMed PubMed Central

5. Ellulu, MS, Patimah, I, Khaza’ai, H, Rahmat, A, Abed, Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci 2017;13:851–63. https://doi.org/10.5114/aoms.2016.58928.Search in Google Scholar PubMed PubMed Central

6. Wallace, AS, Wang, D, Shin, JI, Selvin, E. Screening and diagnosis of prediabetes and diabetes in US children and adolescents. Pediatrics 2020;146. https://doi.org/10.1542/peds.2020-0265.Search in Google Scholar PubMed PubMed Central

7. Iacomino, G, Siani, A. Role of microRNAs in obesity and obesity-related diseases. Genes Nutr 2017;12:1–16. https://doi.org/10.1186/s12263-017-0577-z.Search in Google Scholar PubMed PubMed Central

8. Chen, Y, Huang, T, Yu, Z, Yu, Q, Wang, Y, Hu, J, et al.. The functions and roles of sestrins in regulating human diseases. Cell Mol Biol Lett 2022;27:1–24. https://doi.org/10.1186/s11658-021-00302-8.Search in Google Scholar PubMed PubMed Central

9. Lee, JH, Budanov, AV, Karin, M. Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab 2013;18:792–801. https://doi.org/10.1016/j.cmet.2013.08.018.Search in Google Scholar PubMed PubMed Central

10. Sun, W, Wang, Y, Zheng, Y, Quan, N. The emerging role of sestrin2 in cell metabolism, and cardiovascular and age-related diseases. Aging Dis 2020;11:154. https://doi.org/10.14336/ad.2019.0320.Search in Google Scholar

11. Kumar, A, Dhiman, D, Shaha, C. Sestrins: darkhorse in the regulation of mitochondrial health and metabolism. Mol Biol Rep 2020;47:8049–60. https://doi.org/10.1007/s11033-020-05769-w.Search in Google Scholar PubMed

12. Matthews, DR, Hosker, JP, Rudenski, AS, Naylor, B, Treacher, DF, Turner, RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9. https://doi.org/10.1007/bf00280883.Search in Google Scholar

13. Herzallah, HK, Antonisamy, BR, Shafee, MH, Al-Otaibi, ST. Temporal trends in the incidence and demographics of cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade. Saudi Med J 2019;40:277. https://doi.org/10.15537/smj.2019.3.23585.Search in Google Scholar PubMed PubMed Central

14. Temneanu, O, Trandafir, L, Purcarea, M. Type 2 diabetes mellitus in children and adolescents: a relatively new clinical problem within pediatric practice. J Med Life 2016;9:235.Search in Google Scholar

15. Cui, X, You, L, Zhu, L, Wang, X, Zhou, Y, Li, Y, et al.. Change in circulating microRNA profile of obese children indicates future risk of adult diabetes. Metabolism 2018;78:95–105. https://doi.org/10.1016/j.metabol.2017.09.006.Search in Google Scholar PubMed

16. Companys, J, Gosalbes, MJ, Pla-Pagà, L, Calderón-Pérez, L, Llauradó, E, Pedret, A, et al.. Gut microbiota profile and its association with clinical variables and dietary intake in overweight/obese and lean subjects: a cross-sectional study. Nutrients 2021;13:2032. https://doi.org/10.3390/nu13062032.Search in Google Scholar PubMed PubMed Central

17. Carolan, E, Hogan, AE, Corrigan, M, Gaotswe, G, O’Connell, J, Foley, N, et al.. The impact of childhood obesity on inflammation, innate immune cell frequency, and metabolic microRNA expression. J Clin Endocrinol Metab 2014;99:E474–8. https://doi.org/10.1210/jc.2013-3529.Search in Google Scholar PubMed

18. Zhong, H, Ma, M, Liang, T, Guo, L. Role of microRNAs in obesity-induced metabolic disorder and immune response. J Immunol Res 2018;2018:2835761. https://doi.org/10.1155/2018/2835761.Search in Google Scholar PubMed PubMed Central

19. Castorani, V, Polidori, N, Giannini, C, Blasetti, A, Chiarelli, F. Insulin resistance and type 2 diabetes in children. Ann Pediatr Endocrinol Metab 2020;25:217. https://doi.org/10.6065/apem.2040090.045.Search in Google Scholar PubMed PubMed Central

20. Rehman, K, Akash, MSH. Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? J Biomed Sci 2016;23:1–18. https://doi.org/10.1186/s12929-016-0303-y.Search in Google Scholar PubMed PubMed Central

21. Mohany, KM, Al Rugaie, O, Al-Wutayd, O, Al-Nafeesah, A. Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with/without type 2 diabetes: a case control study. BMC Endocr Disord 2021;21:152. https://doi.org/10.1186/s12902-021-00829-z.Search in Google Scholar PubMed PubMed Central

22. Zhou, Y, Gu, P, Shi, W, Li, J, Hao, Q, Cao, X, et al.. MicroRNA-29a induces insulin resistance by targeting PPARδ in skeletal muscle cells. Int J Mol Med 2016;37:931–8. https://doi.org/10.3892/ijmm.2016.2499.Search in Google Scholar PubMed PubMed Central

23. Palihaderu, P, Mendis, B, Premarathne, J, Dias, W, Yeap, SK, Ho, WY, et al.. Therapeutic potential of miRNAs for type 2 diabetes mellitus: an Overview. Epigenetics Insights 2022;15:25168657221130041. https://doi.org/10.1177/25168657221130041.Search in Google Scholar PubMed PubMed Central

24. Ortega, FJ, Mercader, JM, Moreno-Navarrete, JM, Rovira, O, Guerra, E, Esteve, E, et al.. Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes Care 2014;37:1375–83. https://doi.org/10.2337/dc13-1847.Search in Google Scholar PubMed

25. Su, Q, Kumar, V, Sud, N, Mahato, RI. MicroRNAs in the pathogenesis and treatment of progressive liver injury in NAFLD and liver fibrosis. Adv Drug Deliv Rev 2018;129:54–63. https://doi.org/10.1016/j.addr.2018.01.009.Search in Google Scholar PubMed

26. Yang, YM, Seo, SY, Kim, TH, Kim, SG. Decrease of microRNA‐122 causes hepatic insulin resistance by inducing protein tyrosine phosphatase 1B, which is reversed by licorice flavonoid. Hepatology 2012;56:2209–20. https://doi.org/10.1002/hep.25912.Search in Google Scholar PubMed

27. Wang, R, Hong, J, Cao, Y, Shi, J, Gu, W, Ning, G, et al.. Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults. Eur J Endocrinol 2015;172:291–300. https://doi.org/10.1530/eje-14-0867.Search in Google Scholar

28. Mohany, KM, Al Rugaie, O, Al-Wutayd, O, Al-Nafeesah, A, Saleem, TH. Association between circulating microRNAs 486, 146b and 15b and serum betatrophin levels in obese; type 2 diabetic and non-diabetic children. BMC Endocr Disord 2020;20:1–9. https://doi.org/10.1186/s12902-020-00628-y.Search in Google Scholar PubMed PubMed Central

29. Sundararajan, S, Jayachandran, I, Subramanian, S, Anjana, R, Balasubramanyam, M, Mohan, V, et al.. Decreased Sestrin levels in patients with type 2 diabetes and dyslipidemia and their association with the severity of atherogenic index. J Endocrinol Invest 2021;44:1395–405. https://doi.org/10.1007/s40618-020-01429-9.Search in Google Scholar PubMed

30. Mitra, N, Roya, S, Sara, GS, Ali, J, Fatemeh, A, Maryam, RA, et al.. Evaluation of plasma TRB3 and sestrin 2 levels in obese and normal-weight children. Child Obes 2017;13:409–14. https://doi.org/10.1089/chi.2017.0082.Search in Google Scholar PubMed

31. Chung, HS, Hwang, H-J, Hwang, SY, Kim, NH, Seo, JA, Kim, SG, et al.. Association of serum Sestrin2 level with metabolic risk factors in newly diagnosed drug-naïve type 2 diabetes. Diabetes Res Clin Pract 2018;144:34–41. https://doi.org/10.1016/j.diabres.2018.07.024.Search in Google Scholar PubMed

Received: 2023-07-05

Accepted: 2023-10-28

Published Online: 2023-11-16

Published in Print: 2024-01-29

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Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0320

Keywords for this article

obesity; diabetes; inflammation