title: DNA methylation map in circulating leukocytes mirrors subcutaneous adipose tissue methylation pattern: a genome-wide analysis from non-obese and obese patients.
abstract: The characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip. Data were compared between samples from obese (n = 45) and non-obese (n = 8-10) patients by Wilcoxon-rank test, unadjusted for cell type distributions. A global hypomethylation of the differentially methylated CpG sites (DMCpGs) was observed in the obese subcutaneous adipose tissue and leukocytes. The overlap analysis yielded a number of genes mapped by the common DMCpGs that were identified to reflect the obesity state in the leukocytes. Specifically, the methylation levels of FGFRL1, NCAPH2, PNKD and SMAD3 exhibited excellent and statistically significant efficiencies in the discrimination of obesity from non-obesity status (AUC > 0.80; p < 0.05) and a great correlation between both tissues. Therefore, the current study provided new and valuable DNA methylation biomarkers of obesity-related adipose tissue pathogenesis through peripheral blood analysis, an easily accessible and minimally invasive biological material instead of adipose tissue.
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Catalonia, Spain.|Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.
authors.forename: A B
authors.initials: AB
authors.lastname: Crujeiras
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Catalonia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Diaz-Lagares
authors.affiliation: Laboratory of Personalized Medicine, Epigenomics Unit, Medical Research Institute La Fe, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sandoval
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.|Dpt. Nutrition, Food Sciences and Physiology, University of Navarra (UNAV) and IDISNA, Pamplona, Spain.
authors.forename: F I
authors.initials: FI
authors.lastname: Milagro
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.|Dpt. Nutrition, Food Sciences and Physiology, University of Navarra (UNAV) and IDISNA, Pamplona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Navas-Carretero
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Carreira
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Catalonia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gomez
authors.affiliation: Biostatistics Unit, Medical Research Institute La Fe, Valencia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Hervas
authors.affiliation: Clinical and Experimental Endocrinology, Dept of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), ICBAS, University of Porto, Portugal.
authors.forename: M P
authors.initials: MP
authors.lastname: Monteiro
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.
authors.forename: F F
authors.initials: FF
authors.lastname: Casanueva
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Catalonia, Spain.|Institucio Catalana de Recerca i Estudis Avançats (ICREA); Passeig de Lluís Companys, 23, Barcelona, Catalonia, Spain.|Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Esteller
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.|Dpt. Nutrition, Food Sciences and Physiology, University of Navarra (UNAV) and IDISNA, Pamplona, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Martinez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015894:Genome, Human; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D051500:Receptor, Fibroblast Growth Factor, Type 5 / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics; D050151:Subcutaneous Fat / Q000378:metabolism*
chemical_list: C417531:FGFRL1 protein, human; D009124:Muscle Proteins; C495444:PNKD protein, human; D051500:Receptor, Fibroblast Growth Factor, Type 5; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C472564:PRSS27 protein, human; D012697:Serine Endopeptidases