title: DNA Methylation and Hydroxymethylation Levels in Relation to Two Weight Loss Strategies: Energy-Restricted Diet or Bariatric Surgery.
abstract: BACKGROUND
  Weight loss can be influenced by genetic factors and epigenetic mechanisms that participate in the regulation of body weight. This study aimed to investigate whether the weight loss induced by two different obesity treatments (energy restriction or bariatric surgery) may affect global DNA methylation (LINE-1) and hydroxymethylation profile, as well as the methylation patterns in inflammatory genes.
  
  
  METHODS
  This study encompassed women from three differents groups: 1. control group (n = 9), normal weight individuals; 2. energy restriction group (n = 22), obese patients following an energy-restricted Mediterranean-based dietary treatment (RESMENA); and 3. bariatric surgery group (n = 14), obese patients underwent a hypocaloric diet followed by bariatric surgery. Anthropometric measurements and 12-h fasting blood samples were collected before the interventions and after 6 months. Lipid and glucose biomarkers, global hydroxymethylation (by ELISA), LINE-1, SERPINE-1, and IL-6 (by MS-HRM) methylation levels were assessed in all participants.
  
  
  RESULTS
  Baseline LINE-1 methylation was associated with serum glucose levels whereas baseline hydroxymethylation was associated with BMI, waist circumference, total cholesterol, and triglycerides. LINE-1 and SERPINE-1 methylation levels did not change after weight loss, whereas IL-6 methylation increased after energy restriction and decreased in the bariatric surgery group. An association between SERPINE-1 methylation and weight loss responses was found.
  
  
  CONCLUSIONS
  Global DNA methylation and hydroxymethylation might be biomarkers for obesity and associated comorbidities. Depending on the obesity treatment (diet or surgery), the DNA methylation patterns behave differently. Baseline SERPINE-1 methylation may be a predictor of weight loss values after bariatric surgery.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. carol_nicolettif@yahoo.com.br.
authors.forename: Carolina Ferreira
authors.initials: CF
authors.lastname: Nicoletti
authors.affiliation: Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. carla@fmrp.usp.br.
authors.forename: Carla Barbosa
authors.initials: CB
authors.lastname: Nonino
authors.affiliation: Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. bruno_parenti@hotmail.com.
authors.forename: Bruno Affonso Parenti
authors.initials: BA
authors.lastname: de Oliveira
authors.affiliation: Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. marcelapinhel@yahoo.com.br.
authors.forename: Marcela Augusta de Souza
authors.initials: MA
authors.lastname: Pinhel
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, c/Irunlarrea 1, 31008, Pamplona, Spain. mlmansego@unav.es.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mansego
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, c/Irunlarrea 1, 31008, Pamplona, Spain. fmilagro@unav.es.|Centre for Nutrition Research, University of Navarra, Pamplona, Spain. fmilagro@unav.es.|CIBERobn Fisiología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. fmilagro@unav.es.
authors.forename: Fermin Ignacio
authors.initials: FI
authors.lastname: Milagro
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, c/Irunlarrea 1, 31008, Pamplona, Spain. mazulet@unav.es.|Centre for Nutrition Research, University of Navarra, Pamplona, Spain. mazulet@unav.es.|CIBERobn Fisiología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. mazulet@unav.es.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. mazulet@unav.es.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Zulet
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, c/Irunlarrea 1, 31008, Pamplona, Spain. jalfmtz@unav.es.|Centre for Nutrition Research, University of Navarra, Pamplona, Spain. jalfmtz@unav.es.|CIBERobn Fisiología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. jalfmtz@unav.es.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. jalfmtz@unav.es.
authors.forename: José Alfredo
authors.initials: JA
authors.lastname: Martinez
mesh_terms: D000328:Adult; D031204:Caloric Restriction; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D015390:Gastric Bypass; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D006900:Hydroxylation; D015850:Interleukin-6 / Q000235:genetics; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008745:Methylation; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000235:genetics* / Q000601:surgery / Q000628:therapy*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D015431:Weight Loss / Q000235:genetics; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C508600:IL6 protein, human; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human
keywords: 5-hmC hydroxymethylation; DNA methylation; LINE-1, IL-6, SERPINE-1; Obesity