The role of circulating miRNAs in leptin resistance in obese children
-
Emre Murat Altınkılıç
,
Selami Bayrakdar
Abstract
Objectives
Leptin resistance is one of the important causes of obesity in children. Besides known causes of leptin resistance like mutations in leptin and leptin receptor genes, overexpression of SOCS3 in arcuate nucleus is a potential cause of leptin resistance. We aimed to determine the effects of circulating miRNAs on leptin resistance in obese children by targeting SOCS3 pathway.
Methods
miRNAs potentially targeting SOCS3 were determined by using online target prediction databases. Polymorphisms in miRNA target sequences were determined by using online genome browsers. miRNA expression levels of obese (n=35) and non-obese (n=30) children were determined by qPCR method, genotyping were performed by real-time PCR method and serum leptin, leptin receptor and SOCS3 levels were measured by ELISA method.
Results
miRNA profiling have shown that serum miR-218-5p levels are significantly (p<0.05) increased in accordance with serum leptin levels in obese children.
Conclusions
In this study we used target prediction methods for evaluating potential miRNAs which may involve in development of leptin resistance. We have shown that miR-218-5p might be taking part in leptin resistance in obese children.
-
Research funding: This study has funded by Yeditepe University.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: All subjects participating in the study and/or their respective legal guardians were informed about the objectives and signed the Informed Consent Form.
-
Ethical approval: The study was approved by Ethical Comittee of Yeditepe University.
References
1. Myers, MG, Leibel, RL, Seeley, RJ, Schwartz, MW. Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metabol 2010;21:643–51.10.1016/j.tem.2010.08.002Suche in Google Scholar PubMed PubMed Central
2. Myers, MG, Cowley, MA, Münzberg, H. Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 2008;70:537–56.10.1146/annurev.physiol.70.113006.100707Suche in Google Scholar PubMed
3. Gruzdeva, O, Borodkina, D, Uchasova, E, Dyleva, Y, Barbarash, O. Leptin resistance: underlying mechanisms and diagnosis. Diabetes Metab Syndr Obes 2019;12:191–8.10.2147/DMSO.S182406Suche in Google Scholar PubMed PubMed Central
4. Babon, JJ, Nicola, NA. The biology and mechanism of action of suppressor of cytokine signaling 3. Growth Factors 2012;30:207–19.10.3109/08977194.2012.687375Suche in Google Scholar PubMed PubMed Central
5. Bjørbæk, C, El-Haschimi, K, Frantz, JD, Flier, JS. The role of SOCS-3 in leptin signaling and leptin resistance. J Biol Chem 1999;274:30059–65.10.1074/jbc.274.42.30059Suche in Google Scholar PubMed
6. Mori, H, Hanada, R, Hanada, T, Aki, D, Mashima, R, Nishinakamura, H, et al.. Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 2004;10:739–43.10.1038/nm1071Suche in Google Scholar PubMed
7. https://mirtarbase.cuhk.edu.cn/∼miRTarBase/miRTarBase_2022/php/search.php?org=hsa&mirnas=&targets=SOCS3%2C+LEP%2C+LEPR&opt=adv.Suche in Google Scholar
8. https://www.targetscan.org/cgi-bin/targetscan/vert_80/targetscan.cgi?species=Human&gid=&mir_sc=&mir_c=&mir_nc=&mir_vnc=&mirg=hsa-miR-218-5p.Suche in Google Scholar
9. https://www.mirbase.org/cgi-bin/mature.pl?acc=MIMAT0000275.Suche in Google Scholar
10. https://www.ncbi.nlm.nih.gov/gene/9021.Suche in Google Scholar
11. https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr17%3A78356778%2D78360077&hgsid=1331103707_57S1CKAvFIGG6SOZPu5CFQJO5sWA.Suche in Google Scholar
12. Martinelli, R, Nardelli, C, Pilone, V, Buonomo, T, Liguori, R, Castanò, I, et al.. miR-519d overexpression is associated with human obesity. Obesity 2010;18:2170–6.10.1038/oby.2009.474Suche in Google Scholar PubMed
13. Heneghan, HM, Miller, N, Kerin, MJ. Role of microRNAs in obesity and the metabolic syndrome. Obes Rev 2010;11:354–61.10.1111/j.1467-789X.2009.00659.xSuche in Google Scholar PubMed
14. Arner, P, Kulyté, A. MicroRNA regulatory networks in human adipose tissue and obesity. Nat Rev Endocrinol 2015;11:276–88.10.1038/nrendo.2015.25Suche in Google Scholar PubMed
15. Heneghan, HM, Miller, N, McAnena, OJ, O’Brien, T, Kerin, MJ. Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers. J Clin Endocrinol Metab 2011;96:E846–50.10.1210/jc.2010-2701Suche in Google Scholar PubMed
16. Myers, MG, Leibel, RL, Seeley, RJ, Schwartz, MW. Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metabol 2010;21:643–51.10.1016/j.tem.2010.08.002Suche in Google Scholar PubMed PubMed Central
17. Hassink, SG, Sheslow, DV, de Lancey, E, Opentanova, I, Considine, RV, Caro, JF. Serum leptin in children with obesity: relationship to gender and development. Pediatrics 1996;98:201–3.10.1542/peds.98.2.201Suche in Google Scholar
18. Abdul Wahab, A, Maarafiya, MM, Soliman, A, Younes, NBM, Chandra, P. Serum leptin and adiponectin levels in obese and nonobese asthmatic school children in relation to asthma control. J Allergy 2013;2013:654104.10.1155/2013/654104Suche in Google Scholar PubMed PubMed Central
19. Prats-Puig, A, Ortega, FJ, Mercader, JM, Moreno-Navarrete, JM, Moreno, M, Bonet, N, et al.. Changes in circulating microRNAs are associated with childhood obesity. J Clin Endocrinol Metab 2013;98:E1655–60.10.1210/jc.2013-1496Suche in Google Scholar PubMed
20. Khalyfa, A, Gozal, D. Exosomal miRNAs as potential biomarkers of cardiovascular risk in children. J Transl Med 2014;12:162.10.1186/1479-5876-12-162Suche in Google Scholar PubMed PubMed Central
21. Can, U, Buyukinan, M, Yerlikaya, FH. The investigation of circulating microRNAs associated with lipid metabolism in childhood obesity. Pediat Obes 2016;11:228–34.10.1111/ijpo.12050Suche in Google Scholar PubMed
22. 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;78:95–105.10.1016/j.metabol.2017.09.006Suche in Google Scholar PubMed
23. Zastrow, O, Seidel, B, Kiess, W, Thiery, J, Keller, E, Böttner, A, et al.. The soluble leptin receptor is crucial for leptin action: evidence from clinical and experimental data. Int J Obes Relat Metab Disord 2003;27:1472–8.10.1038/sj.ijo.0802432Suche in Google Scholar PubMed
© 2022 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review Articles
- The genetic elucidation of monogenic obesity in the Arab world: a systematic review
- Global perspective on pediatric growth hormone registries: a systematic review
- Mini Review
- Considering metformin as a second-line treatment for children and adolescents with prediabetes
- Original Articles
- Central adrenal insufficiency screening with morning plasma cortisol and ACTH levels in Prader–Willi syndrome
- Clinical characteristics and genetics analysis for the ITD of congenital hypothyroidism
- Genomic landscape of sporadic pediatric differentiated thyroid cancers: a systematic review and meta-analysis
- The role of circulating miRNAs in leptin resistance in obese children
- Relationship between height age, bone age and chronological age in normal children in the context of nutritional and pubertal status
- Clinical, biochemical, and biomolecular aspects of congenital adrenal hyperplasia in a group of Cameroonian children and adolescents
- Ten year analysis of the clinic profile of the tertiary paediatric endocrine service in Western Australia
- Postoperative intensive care management and residual endocrinopathy of pediatric supratentorial brain tumors: a retrospective cohort study
- Successful telehealth transformation of a pediatric outpatient obesity teaching program due to the COVID-19 pandemic – the “Video KiCK” program
- Glycemic control among children with type 1 diabetes mellitus and its determinants in a resource-limited setting
- Letter to the Editor
- Anxiety, pediatric type 1 diabetes and COVID-19 lockdown
- Short Communication
- Ethnic diversity and burden of polycystic ovary syndrome among US adolescent females
- Case Reports
- Feminizing adrenocortical oncocytoma presenting as precocious puberty: a case report and literature review
- Novel OTX2 loss of function variant associated with congenital hypopituitarism without eye abnormalities
- Bilateral Wilms’ tumor in a child with Denys-Drash syndrome: novel frameshift variant disrupts the WT1 nuclear location signaling region
- A very rare cause of arthrogryposis multiplex congenita: a novel mutation in TOR1A
Artikel in diesem Heft
- Frontmatter
- Review Articles
- The genetic elucidation of monogenic obesity in the Arab world: a systematic review
- Global perspective on pediatric growth hormone registries: a systematic review
- Mini Review
- Considering metformin as a second-line treatment for children and adolescents with prediabetes
- Original Articles
- Central adrenal insufficiency screening with morning plasma cortisol and ACTH levels in Prader–Willi syndrome
- Clinical characteristics and genetics analysis for the ITD of congenital hypothyroidism
- Genomic landscape of sporadic pediatric differentiated thyroid cancers: a systematic review and meta-analysis
- The role of circulating miRNAs in leptin resistance in obese children
- Relationship between height age, bone age and chronological age in normal children in the context of nutritional and pubertal status
- Clinical, biochemical, and biomolecular aspects of congenital adrenal hyperplasia in a group of Cameroonian children and adolescents
- Ten year analysis of the clinic profile of the tertiary paediatric endocrine service in Western Australia
- Postoperative intensive care management and residual endocrinopathy of pediatric supratentorial brain tumors: a retrospective cohort study
- Successful telehealth transformation of a pediatric outpatient obesity teaching program due to the COVID-19 pandemic – the “Video KiCK” program
- Glycemic control among children with type 1 diabetes mellitus and its determinants in a resource-limited setting
- Letter to the Editor
- Anxiety, pediatric type 1 diabetes and COVID-19 lockdown
- Short Communication
- Ethnic diversity and burden of polycystic ovary syndrome among US adolescent females
- Case Reports
- Feminizing adrenocortical oncocytoma presenting as precocious puberty: a case report and literature review
- Novel OTX2 loss of function variant associated with congenital hypopituitarism without eye abnormalities
- Bilateral Wilms’ tumor in a child with Denys-Drash syndrome: novel frameshift variant disrupts the WT1 nuclear location signaling region
- A very rare cause of arthrogryposis multiplex congenita: a novel mutation in TOR1A
