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Epigenetic patterns in successful weight loss maintainers: a pilot study

International Journal of Obesity volume 39, pages 865868 (2015) | Download Citation


DNA methylation changes occur in animal models of calorie restriction, simulating human dieting, and in human subjects undergoing behavioral weight loss interventions. This suggests that obese (OB) individuals may possess unique epigenetic patterns that may vary with weight loss. Here, we examine whether methylation patterns in leukocytes differ in individuals who lost sufficient weight to go from OB to normal weight (NW; successful weight loss maintainers; SWLMs) vs currently OB or NW individuals. This study examined peripheral blood mononuclear cell (PBMC) methylation patterns in NW (n=16, current/lifetime BMI 18.5–24.9) and OB individuals (n=16, current body mass index (BMI)30), and SWLM (n=16, current BMI 18.5–24.9, lifetime maximum BMI 30, average weight loss 57.4 lbs) using an Illumina Infinium HumanMethylation450 BeadArray. No leukocyte population-adjusted epigenome-wide analyses were significant; however, potentially differentially methylated loci across the groups were observed in ryanodine receptor-1 (RYR1; P=1.54E−6), myelin protein zero-like 3 (MPZL3; P=4.70E−6) and alpha 3c tubulin (TUBA3C; P=4.78E−6). In 32 obesity-related candidate genes, differential methylation patterns were found in brain-derived neurotrophic factor (BDNF; gene-wide P=0.00018). In RYR1, TUBA3C and BDNF, SWLM differed from OB but not NW. In this preliminary investigation, leukocyte SWLM DNA methylation patterns more closely resembled NW than OB individuals in three gene regions. These results suggest that PBMC methylation is associated with weight status.

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This research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (grant DK066787 to JMM) and the National Heart, Lung, and Blood Institute (grant T32HL076134-04 to JZJM). JZJM is now at the Penn State College of Medicine Tobacco Center of Regulatory Science (TCORS) and is funded by grant P50-DA-036107-01 from the National Institutes of Health.

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Author notes

    • Y-T Huang
    •  & J Z J Maccani

    These authors contributed equally to this work.


  1. Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA

    • Y-T Huang
    •  & K T Kelsey
  2. Tobacco Center of Regulatory Science, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA

    • J Z J Maccani
  3. Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA

    • N L Hawley
    • , R R Wing
    •  & J M McCaffery
  4. Weight Control and Diabetes Research Center, The Miriam Hospital Weight Control and Diabetes Research Center, Providence, RI, USA

    • N L Hawley
    • , R R Wing
    •  & J M McCaffery
  5. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA

    • N L Hawley
  6. Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA

    • K T Kelsey


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The authors declare no conflict of interest.

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Correspondence to J M McCaffery.

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