title: A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet-induced weight loss.
abstract: Epigenetics could help to explain individual differences in weight loss after an energy-restriction intervention. Here, we identify novel potential epigenetic biomarkers of weight loss, comparing DNA methylation patterns of high and low responders to a hypocaloric diet. Twenty-five overweight or obese men participated in an 8-wk caloric restriction intervention. DNA was isolated from peripheral blood mononuclear cells and treated with bisulfite. The basal and endpoint epigenetic differences between high and low responders were analyzed by methylation microarray, which was also useful in comparing epigenetic changes due to the nutrition intervention. Subsequently, MALDI-TOF mass spectrometry was used to validate several relevant CpGs and the surrounding regions. DNA methylation levels in several CpGs located in the ATP10A and CD44 genes showed statistical baseline differences depending on the weight-loss outcome. At the treatment endpoint, DNA methylation levels of several CpGs on the WT1 promoter were statistically more methylated in the high than in the low responders. Finally, different CpG sites from WT1 and ATP10A were significantly modified as a result of the intervention. In summary, hypocaloric-diet-induced weight loss in humans could alter DNA methylation status of specific genes. Moreover, baseline DNA methylation patterns may be used as epigenetic markers that could help to predict weight loss.
authors.affiliation: Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Pamplona, Spain.
authors.forename: Fermin I
authors.initials: FI
authors.lastname: Milagro
authors.forename: Javier
authors.initials: J
authors.lastname: Campión
authors.forename: Paúl
authors.initials: P
authors.lastname: Cordero
authors.forename: Estíbaliz
authors.initials: E
authors.lastname: Goyenechea
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gómez-Uriz
authors.forename: Itziar
authors.initials: I
authors.lastname: Abete
authors.forename: Maria A
authors.initials: MA
authors.lastname: Zulet
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D031204:Caloric Restriction; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004038:Diet, Reducing; D057890:Epigenomics; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D046228:Microarray Analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D025721:WT1 Proteins / Q000235:genetics*; D015431:Weight Loss / Q000235:genetics*
chemical_list: D015415:Biomarkers; D026901:Membrane Transport Proteins; D025721:WT1 Proteins; D000251:Adenosine Triphosphatases; C426648:ATP10A protein, human