Skip to main content Skip to main navigation menu Skip to site footer
Published: 2021-12-23

Programming of obesity and pediatric metabolic syndromes: a review in light of epigenetic modulation

State Department of Health - Center for Comprehensive Child Care (Secretaria Estadual de Saúde – Centro de Atenção Integral à Criança (CAIC), Dr Afrânio Soares, Manaus, Amazônia, Brazil / Martinho Clinic, Manaus, Amazônia, Brazil
DNA methylation miRNAs Epigenetic programming Metabolic comorbidities Adiposity


Obesity is a multifactorial health problem characterized by the excessive accumulation of fat in the body and affects approximately 338 million children and adolescents worldwide. For this reason, this study consisted of a literature review to investigate how the causes and treatments of pediatric obesity are being addressed in light of epigenetic modulation as a factor in metabolic programming. For this, preferentially original articles published in English between the years 2017 to 2021 in the PubMed and Scholar Google databases were searched using the epigenetics descriptors; epigenetic modulation; child obesity; metabolic syndrome, combined with each other. A total of 54,000 articles were returned to searches in PubMed and 16,107,000 in Scholar Google. Fewer than 500 studies jointly addressed epigenetics and aspects of obesity or metabolic syndromes in childhood. Only 14 works matched the search criteria. The most discussed epigenetic mechanism in the literature is DNA methylation, whose rates observed mainly in CpG islands of promoter regions in several genes contribute to the prevention and early diagnosis of obesity and other pediatric comorbidities even before birth, based on the correlation between the epigenetic marks, maternal and paternal health and anthropometric indices. Although experimental studies on infant metabolic programming are scarce, existing knowledge suggests that environmental, nutritional, and energy expenditure changes are capable of modulating the epigenome and reversing marks that induce susceptibility to metabolic comorbidities.


  1. World Health Organization. "Overweightandobesity." (2020).
  2. Angoorani P, Heshmat R, Ejtahed HS, Motlagh ME, Ziaodini H, Taheri M, et al. Validity of triglyceride–glucose index as an indicator for metabolic syndrome in children and adolescents: the CASPIAN-V study. Eat Weight Disord. 2018;23(6):877–83. Available from:
  3. Weihrauch-Blüher S, Schwarz P, Klusmann JH. Childhood obesity: increased risk for cardiometabolic disease and cancer in adulthood. Metabolism. 2019;92:147–52. Available from:
  4. Chait A, den Hartigh LJ. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front Cardiovasc Med. 2020;7:1–41.
  5. Halldorsdottir T, Binder EB. Gene × Environment Interactions: From Molecular Mechanisms to Behavior. Annu Rev Psychol. 2017;68:215–41.
  6. Schaefer GB, Thompson J. Genética médica: uma abordagem integrada. AMGH Editora; 2015.
  7. Méndez-Mancilla A, Lima-Rogel V, Toro-Ortíz JC, Escalante-Padrón F, Monsiváis-Urenda AE, Noyola DE, et al. Differential expression profiles of circulating microRNAs in newborns associated to maternal pregestational overweight and obesity. Pediatr Obes. 2018;13(3):168–74.
  8. Dunford AR, Sangster JM. Maternal and paternal periconceptional nutrition as an indicator of offspring metabolic syndrome risk in later life through epigenetic imprinting: A systematic review. Diabetes Metab Syndr Clin Res Rev. 2017;11:S655–62. Available from:
  9. Martin CL, Jima D, Sharp GC, McCullough LE, Park SS, Gowdy KM, et al. Maternal pre- pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study. Epigenetics. 2019;14(4):325–40. Available from:
  10. Noor N, Cardenas A, Rifas-Shiman SL, Pan H, Dreyfuss JM, Oken E, et al. Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood. JAMA Netw open. 2019;2(12):e1916777.
  11. Yang I V., Zhang W, Davidson EJ, Fingerlin TE, Kechris K, Dabelea D. Epigenetic marks of in utero exposure to gestational diabetes and childhood adiposity outcomes: the EPOCH study. Diabet Med. 2018;35(5):612–20.
  12. Liu X, Liu X, Shi Q, Fan X, Qi K. Association of telomere length and telomerase methylation with n-3 fatty acids in preschool children with obesity. BMC Pediatr. 2021;21(1):1–8.
  13. Koh IU, Choi NH, Lee K, Yu HY, Yun JH, Kong JH, et al. Obesity susceptible novel DNA methylation marker on regulatory region of inflammation gene: Results from the Korea Epigenome Study (KES). BMJ Open Diabetes Res Care. 2020;8(1):1–10.
  14. Rzehak P, Covic M, Saffery R, Reischl E, Wahl S, Grote V, et al. DNA-Methylation and Body Composition in Preschool Children: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study. Sci Rep. 2017;7(1):1–13. Available from:
  15. Samblas M, Milagro FI, Mansego ML, Marti A, Martinez JA. PTPRS and PER3 methylation levels are associated with childhood obesity: results from a genome-wide methylation analysis. Pediatr Obes. 2018;13(3):149–58.
  16. Gallardo-Escribano C, Buonaiuto V, Ruiz-Moreno MI, Vargas-Candela A, Vilches-Perez A, Benitez-Porres J, et al. Epigenetic approach in obesity: DNA methylation in a prepubertal population which underwent a lifestyle modification. Clin Epigenetics. 2020;12(1):1–14.
  17. He F, Berg A, Imamura Kawasawa Y, Bixler EO, Fernandez-Mendoza J, Whitsel EA, et al. Association between DNA methylation in obesity-related genes and body mass index percentile in adolescents. Sci Rep. 2019;9(1):1–8. Available from:
  18. Czogała W, Czogała M, Strojny W, Watorą G, Wołkow P, Wójcik M, et al. Methylation and expression of FTO and PLAG1 genes in childhood obesity: Insight into anthropometric parameters and glucose–lipid metabolism. Nutrients. 2021;13(5):1–19.
  19. Fradin D, Boëlle PY, Belot MP, Lachaux F, Tost J, Besse C, et al. Genome-Wide Methylation Analysis Identifies Specific Epigenetic Marks in Severely Obese Children. Sci Rep. 2017;7(November 2016):1–8.
  20. Lillycrop K, Murray R, Cheong C, Teh AL, Clarke-Harris R, Barton S, et al. ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity. EBioMedicine. 2017;19:60–72. Available from:

How to Cite

Martinho, L. C. A. P. (2021). Programming of obesity and pediatric metabolic syndromes: a review in light of epigenetic modulation. International Journal of Nutrology, 15(1).