Overweight is associated with lower NR3C1 dna methylation in adults

Introduction: epigenetic alterations in glucocorticoid receptor gene (NR3C1) have been associated with psychosocial stress, however, their potential role in obesity remains unclear. Objective: given the complex interplay between psychosocial stress, HPA axis dysregulation, and obesity, the aim of this study was to investigate the association between overweight status and NR3C1 DNA methylation in adults. Methods: this study was characterized as a cross-sectional analysis. Two hundred and eighty-two Brazilian adults aged between 20 and 59 years were recruited from a public primary health care service. Participants underwent an anthropometric assessment. Venous blood samples were collected and NR3C1 DNA methylation was quantified using pyrosequencing. The association between overweight and NR3C1 DNA methylation was assessed using Mann-Whitney U test, Spearman correlation test and multivariable Poisson regression with robust variance (p<0,05). Results: the overweight group had lower DNA methylation levels than the non-overweight group for both total and CpG site-specific methylation (p <0.05 and p corrected= 0.037). Through factor analysis, two bins of CpGs were extracted, which were intercorrelated. The low methylation in these bins and in the total segment was explained by overweight status, controlled by confounding variables. Conclusion: this is one of the first studies to suggest an involvement between weight accumulation and methylation changes in NR3C1, a complex gene that encodes the glucocorticoid receptor and regulates stress responsiveness.