Research Article

Expression of Circulating MicroRNAs Associated with Obesity and their Relationships with Biochemical Parameters and Health-related Physical Fitness in Children 6 to 10 Years Old in Cali, Colombia

Author(s): Carlos Andrés Rico-Flórez, Daniel Solis-Toro, Ana Maria Arboleda, Ángela Hoyos-Quintero, Diego Bravo-Solarte, Blanca Salazar, Harry Garcia, Jose Guillermo Ortega, Milton Fabián Suaréz- Ortegón, Santiago Arboleda-Franco and Mildrey Mosquera Escudero*

Volume 12, Issue 1, 2023

Published on: 12 January, 2023

Page: [45 - 62] Pages: 18

DOI: 10.2174/2211536612666221205144321

Price: $65

Abstract

Background: Obesity is a public health problem worldwide; it has reached pandemic proportions in the last 40 years. Its prevalence in children and adolescents increased from 0.7% to 7.8% between 1975 and 2016. Recently, microRNAs (miRNAs) have been reported as regulatory factors related to molecular functions under different conditions. These can be used as biomarkers of a disease to estimate risks in the early stages.

Objective: This study aimed to determine the expression levels of miRNAs associated with childhood obesity and their relationships with biochemical parameters and Health-related Physical Fitness (HRPF).

Methods: This was a descriptive cross-sectional study in which a population of 40 children between 6 and 10 years of age of both sexes from Cali, Colombia, was evaluated; the children were classified as 20 normal-weight and 20 obese. Blood biochemistry, HRPF, and miRNA expression levels were determined (hsa-miR-122-5p, hsa-miR-15b-5p, hsa-miR-191-5p, hsa-miR-486-3p, hsa-miR-222-3p. Comparisons were made between the groups, miRNA associations between the studied variables, and linear regression analysis.

Results: Twenty normal-weight and 20 obese patients were evaluated. Both groups had an average age of eight years old. The miRNA hsa-miR-122-5p (p < 0.05) was overexpressed in the obese group. According to the linear regression analysis, the amount of adipose tissue may be associated with the production of miRNAs (hsa-miR-15b-5p, hsa-miR-222-3p, hsa-miR-122-5p, and hsamiR- 191-5p).

Conclusion: Four miRNAs (hsa-miR-15b-5p, hsa-miR-222-3p, hsa-miR-122-5p, and hsa-miR- 191-5p) are associated with modifications in biochemical variables of HRPF in this group. Adipose tissue mass could be associated with the production of these miRNAs, thus making them biomarkers of childhood obesity risk.

Keywords: Circulating microRNA, obesity, biomarkers, physical fitness, HRPF, body mass index.

Graphical Abstract
[1]
WHO Consultation on Obesity (1999: Geneva, Switzerland) & World Health Organization. (2000). Obesity: preventing and managing the global epidemic : report of a WHO consultation. World Health Organization. [https://apps.who.int/iris/handle/10665/42330
[2]
Abarca-Gómez L, Abdeen ZA, Hamid ZA, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 2017; 390(10113): 2627-42.
[http://dx.doi.org/10.1016/S0140-6736(17)32129-3] [PMID: 29029897]
[3]
Di Cesare M, Bentham J, Stevens GA, Zhou B, Danaei G, Lu Y. Trends in adult body-mass index in 200 countries from 1975 to 2014: A pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 2016; 387(10026): 1377-96.
[http://dx.doi.org/10.1016/S0140-6736(16)30054-X] [PMID: 27115820]
[4]
World Health Organization.Obesity and Overweight. 2016. Available from: [https://www.who.int/mediacentre/factsheets/fs311/en
[5]
ICBF, Ministry of Health and Social protection, National Health Institute National Survey of Nutritional Situation ENSIN. 2015. Available from: [https://www.icbf.gov.co/bienestar/nutricion/encuesta-nacional-situacion-nutricional#ensin1
[6]
Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA 2003; 289(2): 187-93.
[http://dx.doi.org/10.1001/jama.289.2.187] [PMID: 12517229]
[7]
Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med 2010; 363(23): 2211-9.
[http://dx.doi.org/10.1056/NEJMoa1000367] [PMID: 21121834]
[8]
Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: Collaborative analyses of 57 prospective studies. Lancet 2009; 373(9669): 1083-96.
[http://dx.doi.org/10.1016/S0140-6736(09)60318-4] [PMID: 19299006]
[9]
Singh GM, Danaei G, Farzadfar F, et al. The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: A pooled analysis. PLoS One 2013; 8(7): e65174.
[http://dx.doi.org/10.1371/journal.pone.0065174] [PMID: 23935815]
[10]
Wormser D, Kaptoge S, Di Angelantonio E, et al. Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: Collaborative analysis of 58 prospective studies. Lancet 2011; 377(9771): 1085-95.
[http://dx.doi.org/10.1016/S0140-6736(11)60105-0] [PMID: 21397319]
[11]
Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003; 81(9): 646-56.
[PMID: 14710506]
[12]
Rankin J, Matthews L, Cobley S, et al. Psychological consequences of childhood obesity: Psychiatric comorbidity and prevention. Adolesc Health Med Ther 2016; 7: 125-46.
[http://dx.doi.org/10.2147/AHMT.S101631] [PMID: 27881930]
[13]
Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. Body fatness and cancer—viewpoint of the IARC Working Group. N Engl J Med 2016; 375(8): 794-8.
[http://dx.doi.org/10.1056/NEJMsr1606602] [PMID: 27557308]
[14]
Goran MI, Ball GDC, Cruz ML. Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J Clin Endocrinol Metab 2003; 88(4): 1417-27.
[http://dx.doi.org/10.1210/jc.2002-021442] [PMID: 12679416]
[15]
Vienberg S, Geiger J, Madsen S, Dalgaard LT. MicroRNAs in metabolism. Acta Physiol 2017; 219(2): 346-61.
[http://dx.doi.org/10.1111/apha.12681] [PMID: 27009502]
[16]
Peng C, Wang YL. MicroRNAs as new players in endocrinology. Front Endocrinol 2018; 9: 459.
[http://dx.doi.org/10.3389/fendo.2018.00459] [PMID: 30174649]
[17]
Zhuang G, Meng C, Guo X, et al. A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation. Circulation 2012; 125(23): 2892-903.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.087817] [PMID: 22580331]
[18]
Deiuliis JA. MicroRNAs as regulators of metabolic disease: Pathophysiologic significance and emerging role as biomarkers and therapeutics. Int J Obes 2016; 40(1): 88-101.
[http://dx.doi.org/10.1038/ijo.2015.170] [PMID: 26311337]
[19]
Carolan E, Hogan AE, Corrigan M, et al. The impact of childhood obesity on inflammation, innate immune cell frequency, and metabolic microRNA expression. J Clin Endocrinol Metab 2014; 99(3): E474-8.
[http://dx.doi.org/10.1210/jc.2013-3529] [PMID: 24423308]
[20]
Olivo-Marston SE, Hursting SD, Perkins SN, et al. Effects of calorie restriction and diet-induced obesity on murine colon carcinogenesis, growth and inflammatory factors, and microRNA expression. PLoS One 2014; 9(4): e94765.
[http://dx.doi.org/10.1371/journal.pone.0094765] [PMID: 24732966]
[21]
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75(5): 843-54.
[22]
Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993; 75(5): 855-62.
[http://dx.doi.org/10.1016/0092-8674(93)90530-4] [PMID: 8252622]
[23]
Friedman RC, Farh KKH, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009; 19(1): 92-105.
[http://dx.doi.org/10.1101/gr.082701.108] [PMID: 18955434]
[24]
Weber JA, Baxter DH, Zhang S, et al. The microRNA spectrum in 12 body fluids. Clin Chem 2010; 56(11): 1733-41.
[http://dx.doi.org/10.1373/clinchem.2010.147405] [PMID: 20847327]
[25]
Sayed D, Abdellatif M. MicroRNAs in development and disease. Physiol Rev 2011; 91(3): 827-7.
[http://dx.doi.org/10.1152/physrev.00006.2010] [PMID: 21742789]
[26]
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(5): E846-50.
[http://dx.doi.org/10.1210/jc.2010-2701] [PMID: 21367929]
[27]
Larabee CM, Neely OC, Domingos AI. Obesity: A neuroimmunometabolic perspective. Nat Rev Endocrinol 2020; 16(1): 30-43.
[http://dx.doi.org/10.1038/s41574-019-0283-6] [PMID: 31776456]
[28]
WHO. Growth reference data for 5 -19 years. 2007. Available from: [https://www.who.int/tools/growth-reference-data-for-5to19-years
[29]
Ruiz JR, Castro-Piñero J, España-Romero V, Artero EG, Ortega FB, Cuenca MM. Field-based fitness assessment in young people: The ALPHA health-related fitness test battery for children and adolescents. Br J Sports Med 2010. bjsports75341
[PMID: 20961915]
[30]
Ruíz JR, España Romero V, Castro Piñero J, et al. Alpha-Fitness battery: Field test for the evaluation of physical condition related to health in children and adolescents. Nutr Hosp 2011; 26(6): 1210-4.
[PMID: 22411362]
[31]
Slaughter MH, Lohman TG, Boileau RA, et al. Skinfold equations for estimation of body fatness in children and youth. Hum Biol 1988; 60(5): 709-23.
[PMID: 3224965]
[32]
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and? cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28(7): 412-9.
[http://dx.doi.org/10.1007/BF00280883] [PMID: 3899825]
[33]
Léger LA, Mercier D, Gadoury C, Lambert J. The multistage 20 metre shuttle run test for aerobic fitness. J Sports Sci 1988; 6(2): 93-101.
[http://dx.doi.org/10.1080/02640418808729800] [PMID: 3184250]
[34]
Flórez CAR, García-Perdomo HA, Escudero MM. MicroRNAs associated with overweight and obesity in childhood: A systematic review. MicroRNA 2021; 9(4): 255-65.
[http://dx.doi.org/10.2174/2211536609666191209152721] [PMID: 31814558]
[35]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 2001; 25(4): 402-8.
[36]
Yang WM, Jeong HJ, Park SW, Lee W. Obesity-induced miR-15b is linked causally to the development of insulin resistance through the repression of the insulin receptor in hepatocytes. Mol Nutr Food Res 2015; 59(11): 2303-14.
[http://dx.doi.org/10.1002/mnfr.201500107] [PMID: 26179126]
[37]
Pescador N, Pérez-Barba M, Ibarra JM, Corbatón A, Martínez-Larrad MT, Serrano-Ríos M. Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers. PLoS One 2013; 8(10): e77251.
[http://dx.doi.org/10.1371/journal.pone.0077251] [PMID: 24204780]
[38]
Kim NH, Ahn J, Choi YM, et al. Differential circulating and visceral fat microRNA expression of non-obese and obese subjects. Clin Nutr 2020; 39(3): 910-6.
[http://dx.doi.org/10.1016/j.clnu.2019.03.033] [PMID: 31003790]
[39]
Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 2006; 3(2): 87-98.
[http://dx.doi.org/10.1016/j.cmet.2006.01.005] [PMID: 16459310]
[40]
Elmén J, Lindow M, Schütz S, et al. LNA-mediated microRNA silencing in non-human primates. Nature 2008; 452(7189): 896-9.
[http://dx.doi.org/10.1038/nature06783] [PMID: 18368051]
[41]
Wang R, Hong J, Cao Y, et al. Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults. Eur J Endocrinol 2015; 172(3): 291-300.
[http://dx.doi.org/10.1530/EJE-14-0867] [PMID: 25515554]
[42]
Naeli P, Mirzadeh Azad F, Malakootian M, Seidah NG, Mowla SJ. Post-transcriptional regulation of PCSK9 by miR-191, miR-222, and miR-224. Front Genet 2017; 8: 189.
[http://dx.doi.org/10.3389/fgene.2017.00189] [PMID: 29230236]
[43]
Zhang C, Wang P, Mohammed A, Zhou Z, Zhang S, Ni S. Function of adipose-derived mesenchymal stem cells in monocrotalineinduced pulmonary arterial hypertension through miR-191 via regulation of BMPR2. BioMed research international 2019; 2019: 2858750.
[http://dx.doi.org/10.1155/2019/2858750]
[44]
Bye A, Røsjø H, Aspenes ST, Condorelli G, Omland T, Wisløff U. Circulating microRNAs and aerobic fitness - the hunt study. PLoS One 2013; 8(2): e57496.
[http://dx.doi.org/10.1371/journal.pone.0057496] [PMID: 23469005]
[45]
Bao F, Slusher AL, Whitehurst M, Huang CJ. Circulating microRNAs are upregulated following acute aerobic exercise in obese individuals. Physiol Behav 2018; 197: 15-21.
[http://dx.doi.org/10.1016/j.physbeh.2018.09.011] [PMID: 30248300]
[46]
Li D, Song H, Shuo L, et al. Gonadal white adipose tissue-derived exosomal MiR-222 promotes obesity-associated insulin resistance. Aging 2020; 12(22): 22719-43.
[http://dx.doi.org/10.18632/aging.103891] [PMID: 33197889]

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