Association of weight regain with specific methylation levels in the NPY and POMC promoters in leukocytes of obese men: A translational study

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) 32 weeks 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 +136 bp and +138 bp (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 +136 bp and +138 bp 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. (C) 2013 Elsevier B.V. All rights reserved.