ENDOTHELIAL DYSFUNCTION - AN EARLY MARKER OF CARDIOVASCULAR DAMAGE IN CHILDREN WITH OBESITY
Abstract
Endothelial dysfunction is the leading syndrome and indicator of cardiovascular disease progression in children with obesity. The article discusses the prognostic significance of determining the level of trimethylamine N-oxide (TMAO) in endothelial dysfunction, which will allow timely prevention of cardiovascular complications. The aim of the study: to determine early markers of endothelial dysfunction in children and adolescents with abdominal obesity and to assess the factors of cardiovascular risk development. Materials and methods: 55 children and adolescents with abdominal obesity aged 7-18 years were examined. All underwent anthropometric, general clinical and biochemical studies of the lipid and carbohydrate spectrum. The level of trimethylamine N-oxide (TMAO) was determined in plasma by enzyme-linked immunosorbent assay (ELISA). Study results: A relationship was found between the level of TMAO in body weight and the degree of obesity. A positive correlation between the WC /OB ratio and the TMAO level was noted. When analyzing the correlation parallels between the TMAO level and the carbohydrate and lipid metabolism indices, it was determined with the levels of insulin resistance and HDL-C. Conclusion: Elevated TMAO levels in abdominal obesity in children suggest its contribution to the subsequent development of cardiovascular risk complications.
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List of references
Brunt VE, Casso AG, Gioscia-Ryan RA, et al. Gut microbiome- derived metabolite trimethylamine N-oxide induces aortic stiffening and increases systolic blood pressure with aging in mice and humans. Hypertension. 2021;78(2):499-511. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.120.16895
Canyelles M, Borràs C, Rotllan N, Tondo M, Escolà-Gil JC, Blanco-Vaca F. Gut Microbiota-derived TMAO: a causal factor promoting atherosclerotic cardiovascular disease? Int J Mol Sci. 2023;24(3):1940. DOI: https://doi.org/10.3390/ijms24031940
Chen G, He L, Dou X, Liu T. Association of trimethylamine-N-oxide levels with risk of cardiovascular disease and mortality among elderly subjects: a systematic review and meta-analysis. CardioRenal Med. 2022;12(2):39-54. DOI: https://doi.org/10.1159/000520910
Chen YM, Liu Y, Zhou RF, Chen XL, Wang C, Tan XY, et al. Associations of gutflora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults. Sci Rep (2016) 6:19076. doi: 10.1038/srep19076 DOI: https://doi.org/10.1038/srep19076
Crisci G, Israr MZ, Cittadini A, Bossone E, Suzuki T, Salzano A. Heart failure and trimethylamine N-oxide: time to transform a “gut feeling” in a fact? ESC Heart Fail. 2023;10(1):1-7. DOI: https://doi.org/10.1002/ehf2.14205
de la Monte SM, Tong M, Lawton M, Longato L. Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment. Mol Neurodegener (2009) 4:54. doi: 10.1186/1750-1326-4-54 DOI: https://doi.org/10.1186/1750-1326-4-54
de Quadros Iorra F. et al. Gut Microbiota Metabolite TMAO and Adolescent Cardiometabolic Health: A Cross-sectional Analysis. Journal of the Endocrine Society, 2025, Vol. 9, No. 5. DOI: https://doi.org/10.1210/jendso/bvaf055
Dehghan P, Farhangi MA, Nikniaz L, Nikniaz Z, Asghari-Jafarabadi M. Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) potentially increases the risk of obesity in adults: an explora-tory systematic review and dose-response meta- analysis. Obes Rev. 2020;21(5):e12993. DOI: https://doi.org/10.1111/obr.12993
Gao X, Liu X, Xu J, Xue C, Xue Y, Wang Y. Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet. J Biosci Bioeng (2014) 118(4):476–81. doi: 10.1016/j.jbiosc.2014.03.001 DOI: https://doi.org/10.1016/j.jbiosc.2014.03.001
Li D, Lu Y, Yuan S, et al. Gut microbiota-derived metabolite trimethylamine-N-oxide and multiple health outcomes: an um-brella review and updated meta-analysis. Am J Clin Nutr. 2022;116(1):230-243. DOI: https://doi.org/10.1093/ajcn/nqac074
Li Sy, Chen S, Lu Xt, et al. Serum trimethylamine-N-oxide is asso-ciated with incident type 2 diabetes in middle-aged and older adults: a prospective cohort study. J Transl Med. 2022;20(1):374. DOI: https://doi.org/10.1186/s12967-022-03581-7
Mihuta MS, Paul C, Borlea A, et al. Connections between serum trimethylamine N-oxide (TMAO), a gut-derived metabolite, and vascular biomarkers evaluating arterial stiffness and subclinical atherosclerosis in children with obesity. Front Endocrinol. 2023;14:1253584. DOI: https://doi.org/10.3389/fendo.2023.1253584
Morgan PJ, Young MD, Lloyd AB, Wang ML, Eather N, Miller A, et al. Involvement of fathers in pediatric obesity treatment and prevention trials: a systematic review. Pediatrics. 2017 Feb;139(2). pii: e20162635. DOI: 10.1542/ peds.2016-2635 DOI: https://doi.org/10.1542/peds.2016-2635
Niu Y., Zhao X., He H., Mao X., Sheng J., Zou J., et al. The effect of different adiposity factors on insulin resistance in obese children and adolescents. Clin. Endocrinol. (Oxf). 2021; 94(6): 949–55. https://doi.org/10.1111/cen.14435 DOI: https://doi.org/10.1111/cen.14435
Rastogi S., Rastogi D. The epidemiology and mechanisms of lifetime cardiopulmonary morbidities associated with pre-pregnancy obesity and excessive gestational weight gain. Front. Cardiovasc. Med. 2022; 9: 844905. https://doi.org/10.3389/fcvm.2022.844905 DOI: https://doi.org/10.3389/fcvm.2022.844905
Sarmiento Quintero F, Ariza AJ, Barboza García F, Canal de Molano N, Castro Benavides M, Cruchet Muñoz S, et al. Sobrepeso y obesidad: revisión y puesta al día de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (SLAGHNP). Acta Gastroenterol Latinoam. 2016;46(2):131-159.
Shan Z, Sun T, Huang H, et al. Association between microbiota- dependent metabolite trimethylamine-N-oxide and type 2 diabetes. Am J Clin Nutr. 2017;106(3):888-894. DOI: https://doi.org/10.3945/ajcn.117.157107
Stols-Gonçalves D, Hovingh GK, Nieuwdorp M, Holleboom AG. NAFLD and atherosclerosis: two sides of the same dysmetabolic coin? Trends Endocrinol Metab (2019) 30(12):891–902. doi: 10.1016/j.tem.2019.08.008 DOI: https://doi.org/10.1016/j.tem.2019.08.008
Tang WHW, Bäckhed F, Landmesser U, Hazen SL. Intestinal Microbiota in cardiovascular health and disease. J Am Coll Cardiol. 2019;73(16):2089-2105. DOI: https://doi.org/10.1016/j.jacc.2019.03.024
Tang WHW, Wang Z, Kennedy DJ, et al. Gut Microbiota-dependent trimethylamine N -oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116(3):448-455. DOI: https://doi.org/10.1161/CIRCRESAHA.116.305360
Tang WHW, Wang Z, Levison BS, et al. Intestinal microbial metab-olism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575-1584. DOI: https://doi.org/10.1056/NEJMoa1109400
Tong M, Neusner A, Longato L, Lawton M, Wands JR, de la Monte SM. Nitrosamine exposure causes insulin resistance diseases: relevance to type 2 diabetes mellitus, non-alcoholic steatohepatitis, and Alzheimer's disease. J Alzheimers Dis (2009) 17(4):827–44. doi: 10.3233/JAD-2009-1115. DOI: https://doi.org/10.3233/JAD-2009-1115
Garifulina L. M., Ashurova M. J., Goyibova N. S. Improving the treatment of metabolic syndrome in adolescents through the use of α-lipoic acid.
Рустамов М. Р., Гарифулина Л. М., Бобокулова Г. К. Применение витамина d при ожирении у детей, эффективность влияния на углеводный и липидный обмен //Международный журнал научной педиатрии. – 2025. – Т. 4. – №. 2. – С. 967-971. DOI: https://doi.org/10.56121/2181-2926-2025-4-2-967-971
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