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DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial

Authors
  • Keller, Maria1, 2, 3
  • Yaskolka Meir, Anat4
  • Bernhart, Stephan H.5, 5, 5
  • Gepner, Yftach4, 6
  • Shelef, Ilan7
  • Schwarzfuchs, Dan7, 8
  • Tsaban, Gal4
  • Zelicha, Hila4
  • Hopp, Lydia5
  • Müller, Luise2, 3
  • Rohde, Kerstin1, 2
  • Böttcher, Yvonne3, 9, 10
  • Stadler, Peter F.5, 11, 12, 13, 14, 15, 16
  • Stumvoll, Michael1, 2, 3, 17
  • Blüher, Matthias1, 2
  • Kovacs, Peter2
  • Shai, Iris4
  • 1 Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig, 04103, Germany , Leipzig (Germany)
  • 2 University of Leipzig Medical Center, Leipzig, 04103, Germany , Leipzig (Germany)
  • 3 University of Leipzig, Liebigstrasse 19-21, Leipzig, 04103, Germany , Leipzig (Germany)
  • 4 Ben-Gurion University of the Negev, Beer Sheva, 84105, Israel , Beer Sheva (Israel)
  • 5 University of Leipzig, Leipzig, 04107, Germany , Leipzig (Germany)
  • 6 Tel Aviv University, Ramat Aviv, 6997801, Israel , Ramat Aviv (Israel)
  • 7 Soroka University Medical Center, Beer-Sheva, 84101, Israel , Beer-Sheva (Israel)
  • 8 Nuclear Research Center-Negev, Dimona, 84190, Israel , Dimona (Israel)
  • 9 University of Oslo, Oslo, 0316, Norway , Oslo (Norway)
  • 10 Akershus University Hospital, Lørenskog, 1478, Norway , Lørenskog (Norway)
  • 11 University of Leipzig, Leipzig, 04109, Germany , Leipzig (Germany)
  • 12 Max Planck Institute for Mathematics in the Sciences, Leipzig, 04103, Germany , Leipzig (Germany)
  • 13 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, 04103, Germany , Leipzig (Germany)
  • 14 University of Vienna, Vienna, 1090, Austria , Vienna (Austria)
  • 15 University of Copenhagen, Frederiksberg, 1871, Denmark , Frederiksberg (Denmark)
  • 16 Santa Fe Institute, Santa Fe, NM, 87501, USA , Santa Fe (United States)
  • 17 Deutsches Zentrum für Diabetesforschung, Helmholtz Zentrum München, Neuherberg, 85764, USA , Neuherberg (United States)
Type
Published Article
Journal
Genome Medicine
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Nov 16, 2020
Volume
12
Issue
1
Identifiers
DOI: 10.1186/s13073-020-00794-7
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundOne of the major challenges in obesity treatment is to explain the high variability in the individual’s response to specific dietary and physical activity interventions. With this study, we tested the hypothesis that specific DNA methylation changes reflect individual responsiveness to lifestyle intervention and may serve as epigenetic predictors for a successful weight-loss.MethodsWe conducted an explorative genome-wide DNA methylation analysis in blood samples from 120 subjects (90% men, mean ± SD age = 49 ± 9 years, body mass-index (BMI) = 30.2 ± 3.3 kg/m2) from the 18-month CENTRAL randomized controlled trial who underwent either Mediterranean/low-carbohydrate or low-fat diet with or without physical activity.ResultsAnalyses comparing male subjects with the most prominent body weight-loss (responders, mean weight change − 16%) vs. non-responders (+ 2.4%) (N = 10 each) revealed significant variation in DNA methylation of several genes including LRRC27, CRISP2, and SLFN12 (all adj. P < 1 × 10−5). Gene ontology analysis indicated that biological processes such as cell adhesion and molecular functions such as calcium ion binding could have an important role in determining the success of interventional therapies in obesity. Epigenome-wide association for relative weight-loss (%) identified 15 CpGs being negatively correlated with weight change after intervention (all combined P < 1 × 10− 4) including new and also known obesity candidates such as NUDT3 and NCOR2. A baseline DNA methylation score better predicted successful weight-loss [area under the curve (AUC) receiver operating characteristic (ROC) = 0.95–1.0] than predictors such as age and BMI (AUC ROC = 0.56).ConclusionsBody weight-loss following 18-month lifestyle intervention is associated with specific methylation signatures. Moreover, methylation differences in the identified genes could serve as prognostic biomarkers to predict a successful weight-loss therapy and thus contribute to advances in patient-tailored obesity treatment.

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