title: Association of weight regain with specific methylation levels in the NPY and POMC promoters in leukocytes of obese men: a translational study.
abstract: Specific methylation of appetite-related genes in leukocytes could serve as a useful biomarker to predict weight regain after an energy restriction program. We aimed to evaluate whether the pre-intervention DNA methylation patterns involved in the epigenetic control of appetite-regulatory genes in leukocytes are associated with the weight regain process. Eighteen men who lost ≥5% of body weight after an 8-week nutritional intervention were categorized as "regainers" (≥10% weight regain) and "non-regainers" (<10% weight regain) 32weeks after stopping dieting. At baseline, leukocytes were isolated and DNA was analyzed for epigenetic methylation patterns of appetite-related gene promoters by MALDI-TOF mass spectrometry. Regainers showed higher methylation levels than non-regainers in proopiomelanocortin (POMC) CpG sites +136bp and +138bp (fold change from non-regainers=26%; p=0.020) and lower methylation of the whole analyzed region of neuropeptide Y (NPY; fold change from non-regainers=-22%; p=0.033), as well as of several individual NPY-promoter CpG sites. Importantly, total baseline NPY methylation was associated with weight-loss regain (r=-0.76; p<0.001), baseline plasma ghrelin levels (r=0.60; p=0.011) and leptin/ghrelin ratio (r=-0.52; p=0.046). Lower methylation levels of POMC CpG sites +136bp and +138bp were associated with success in weight-loss maintenance (odds ratio=0.042 [95% CI 0.01-0.57]; p=0.018), whereas lower total methylation levels in NPY promoter were associated with higher risk of weight regain (odds ratio=14.0 [95% CI 1.13-172]; p=0.039). Therefore, the study of leukocyte methylation levels reflects a putative epigenetic regulation of NPY and POMC, which might be implicated in the weight regain process and be used as biomarkers for predicting weight regain after dieting.
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Spain; Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela University (USC), Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Spain. Electronic address: anabelencrujeiras@hotmail.com.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Crujeiras
authors.forename: Javier
authors.initials: J
authors.lastname: Campion
authors.forename: Angel
authors.initials: A
authors.lastname: Díaz-Lagares
authors.forename: Fermin I
authors.initials: FI
authors.lastname: Milagro
authors.forename: Estíbaliz
authors.initials: E
authors.lastname: Goyenechea
authors.forename: Itziar
authors.initials: I
authors.lastname: Abete
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D054439:Ghrelin / Q000097:blood; D006801:Humans; D020738:Leptin / Q000097:blood; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D009478:Neuropeptide Y / Q000097:blood / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000178:diet therapy / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D054411:Receptors, Leptin / Q000235:genetics; D015430:Weight Gain / Q000235:genetics*
chemical_list: D054439:Ghrelin; C515448:LEPR protein, human; D020738:Leptin; D009478:Neuropeptide Y; D054411:Receptors, Leptin; D011333:Pro-Opiomelanocortin
keywords: Blood cells; Epigenetic biomarkers; Ghrelin; Leptin; Obesity