martes, 15 de octubre de 2013

Changes in Circulating MicroRNAs Are Associated With Childhood Obesity

Changes in Circulating MicroRNAs Are Associated With Childhood Obesity


  • JCEM Online: Advances in Genetics



Changes in Circulating MicroRNAs Are Associated With Childhood Obesity












  1. José M. Fernández-Real



- Author Affiliations



  1. Pediatrics Research Group (A.P.-P., A.L.-B.) and Department of Diabetes, Endocrinology, and Nutrition (F.J.O., J.M.M.-N., M.M., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, 17007 Girona, Spain; CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn, CB06/03) (F.J.O., J.M.M.-N., M.M., W.R., J.M.F.-R.), Instituto de Salud Carlos III, 17007 Girona, Spain; Joint Institute for Research and Biomedicine–Barcelona Supercomputing Center Program on Computational Biology (J.M.M.), Barcelona Supercomputing Center, 08028 Barcelona, Spain; and Genome Facility Core Service (N.B.), Universitat Pompeu Fabra, 08003 Barcelona, Spain




  1. Address all correspondence and requests for reprints to: J. M. Fernández-Real, MD, PhD, Section of Diabetes, Endocrinology, and Nutrition. Hospital “Dr Josep Trueta” of Girona, Carretera de França s/n, 17007 Girona, Spain. E-mail: jmfreal@idibgi.org.




  1. * A.P.-P. and F.J.O. contributed equally to the manuscript.






Abstract




Context: Circulating microRNAs (miRNAs) are valuable biomarkers of metabolic diseases and potential therapeutic targets in this field.




Objective: Our objective was to define the circulating pattern of miRNAs in childhood obesity.




Design, Settings, and Main Outcome Measure: The genome-wide circulating miRNA profile was assessed by RT-PCR in 10 boys (5 lean and 5 obese children). The most relevant miRNAs were cross-sectionally validated in 85 lean versus 40 obese children (63 boys and 62 girls) and longitudinally evaluated in samples from the same children when they were ∼7 and ∼10 years old (23 boys and 22 girls).




Results: The cross-sectional validation study disclosed that 15 specific circulating miRNAs were significantly deregulated in prepubertal obesity, including the decreased miR-221 and miR-28-3p and increased concentrations in plasma of miR-486-5p, miR-486-3p, miR-142-3p, miR-130b, and miR-423-5p (all P < .0001). The circulating concentration of these miRNAs was significantly associated with body mass index and other measures of obesity such as percent fat mass, waist, regional fat distribution and with laboratory parameters such as homeostasis model assessment of insulin resistance, high-molecular-weight adiponectin, C-reactive protein, and circulating lipids in concordance with anthropometric associations. Plasma concentrations of 10 of these circulating miRNAs changed significantly and differently during the 3-year follow-up in children who increased or decreased their normalized weight.




Conclusion: This study provides the first evidence that circulating miRNAs are deregulated in prepubertal obese children. Thus, the very early detection of an abnormal circulating miRNA profile may be a promising strategy to identify obese children who may suffer from metabolic abnormalities.





Footnotes




  • Abbreviations:


    BMI

    body mass index

    BP

    blood pressure

    HOMA-IR

    homeostasis model assessment of insulin resistance

    miRNA

    microRNA

    RT

    reverse transcription

    TLDA

    TaqMan miRNA low-density array.





  • Received February 23, 2013.

  • Accepted July 29, 2013.



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