Physical inactivity associated with NR3C1 dna hypermethylation in obesity

Abstract

Introduction: obesity is a major public health issue, linked to chronic stress and metabolic dysregulation. While biological mechanisms of sedentary behavior in obesity are well known, epigenetic factors, particularly those involving the NR3C1 gene, remain unclear, especially in genes related to the regulation of chronic stress and metabolism, such as NR3C1. Objective: this study aimed to investigate the methylation profile of the NR3C1 gene in obese individuals with physical inactivity. Methods: this cross-sectional study included 119 adult volunteers with obesity (BMI ≥30) who accessed public primary health care services. Individuals using glucocorticoids were excluded. Socioeconomic, health, and lifestyle data were collected using structured questionnaires, and depressive symptoms were assessed using the Beck Depression Inventory (BDI-II). Peripheral blood samples were collected in the morning for cortisol quantification and molecular analysis of the NR3C1 gene via pyrosequencing. Multivariate Poisson regression was applied to identify factors associated with physical inactivity. Results: poisson multivariate regression analysis with robust variance showed that physical inactivity was associated with NR3C1 gene hypermethylation at CpGs 44, 45, and 46 in obese individuals and showed that physical inactivity was associated with low cortisol in the obese population. Conclusion: this study suggests an association between a sedentary lifestyle and changes in NR3C1 gene methylation in obese individuals. The association between physical inactivity and low cortisol levels strengthens the hypothesis that a sedentary lifestyle may involve epigenetic action in the dysregulation of the HPA axis of stress adaptation in obese individuals.