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Pediatrics

DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance

Abstract

Objective:

Epigenetic alterations have been suggested to be associated with obesity and related metabolic disorders. Here we examined the correlation between obesity and insulin resistance with the methylation frequency of the leptin (LEP) and adiponectin (ADIPOQ) promoters in obese adolescents with the aim to identify epigenetic markers that might be used as tools to predict and follow up the physiological alterations associated with the development of the metabolic syndrome.

Subjects:

One hundred and six adolescents were recruited and classified according to body mass index and homeostasis model of assessment-insulin resistance index. The circulating concentrations of leptin, adiponectin and of several metabolic markers of obesity and insulin resistance were determined by standard methods. The methylation frequency of the LEP and ADIPOQ promoters was determined by methylation-specific PCR (MS-PCR) in DNA obtained from peripheral blood samples.

Results:

Obese adolescents without insulin resistance showed higher and lower circulating levels of, respectively, leptin and adiponectin along with increased plasmatic concentrations of insulin and triglycerides. They also exhibited the same methylation frequency than lean subjects of the CpG sites located at −51 and −31 nt relative to the transcription start site of the LEP gene. However, the methylation frequency of these nucleotides dropped markedly in obese adolescents with insulin resistance. We found the same inverse relationship between the combined presence of obesity and insulin resistance and the methylation frequency of the CpG site located at −283 nt relative to the start site of the ADIPOQ promoter.

Conclusions:

These observations sustain the hypothesis that epigenetic modifications might underpin the development of obesity and related metabolic disorders. They also validate the use of blood leukocytes and MS-PCR as a reliable and affordable methodology for the identification of epigenetic modifications that could be used as molecular markers to predict and follow up the physiological changes associated with obesity and insulin resistance.

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Acknowledgements

The authors thank the Mexican adolescents and their parents for their participation in the study. We also thank José Alfredo Pérez Ontiveros, Emma Guadalupe Gazcón Morales, Daniel Chavez Vazquez and Sergio Arturo Mavil Cortes for their help with blood sample collection and laboratory measures. We thank Dr. Alfonso Reyes López for his help in analysis. This work was supported by ICyT-DF, SIP-IPN, COFAA-IPN, HIM/2012/002, and CONACyT, Mexico.

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Correspondence to F Bolaños-Jiménez or L A Marchat.

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García-Cardona, M., Huang, F., García-Vivas, J. et al. DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance. Int J Obes 38, 1457–1465 (2014). https://doi.org/10.1038/ijo.2014.30

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  • DOI: https://doi.org/10.1038/ijo.2014.30

Keywords

  • epigenetics
  • DNA methylation
  • childhood obesity
  • insulin resistance
  • leptin
  • adiponectin

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