title: 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.
  
  
  METHODS
  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.
authors.affiliation: Programa de Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, México City, Mexico.
authors.forename: M C
authors.initials: MC
authors.lastname: García-Cardona
authors.affiliation: Laboratorio de Farmacología y Toxicología, Hospital Infantil de México Federico Gómez, México City, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Huang
authors.affiliation: Programa de Biotecnología, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, México City, Mexico.
authors.forename: J M
authors.initials: JM
authors.lastname: García-Vivas
authors.affiliation: Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, México City, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: López-Camarillo
authors.affiliation: Departamento de Alergia, Hospital Infantil de México Federico Gómez, México City, Mexico.
authors.forename: B E
authors.initials: BE
authors.lastname: Del Río Navarro
authors.affiliation: Departamento de Salud Pública, Instituto Nacional de Salud Pública, Cuernavaca Morelos, México City, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Navarro Olivos
authors.affiliation: Departamento de Farmacología, CINVESTAV-IPN, México City, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Hong-Chong
authors.affiliation: INRA, UMR1280 Physiologie des Adaptations Nutritionnelles, Université de Nantes, Nantes Atlantique Université, Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Bolaños-Jiménez
authors.affiliation: 1] Programa de Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, México City, Mexico [2] Programa de Biotecnología, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, México City, Mexico.
authors.forename: L A
authors.initials: LA
authors.lastname: Marchat
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002648:Child; D019175:DNA Methylation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005809:Genes, Regulator; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008800:Mexico; D009765:Obesity / Q000097:blood* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D020738:Leptin