The Epigenetic Role of ADRB3 DNA Methylation in Post-Bariatric Energy Expenditure for Women with Obesity: A Longitudinal Observational Study

Bariatric surgery induces profound metabolic changes that may influence epigenetic mechanisms regulating genes involved in energy metabolism. Given the global burden of obesity on women’s health, understanding sex-specific molecular responses to surgical treatment is essential. This study investigated the effect of Roux-en-Y gastric bypass (RYGB) on DNA methylation of the β-3 adrenergic receptor (ADRB3) gene and its influence on energy expenditure in women with obesity. Sixteen participants were evaluated before and six months after surgery, including measurements of body composition, resting metabolic rate (RMR), and metabolic biomarkers. After RYGB, significant reductions were observed in body weight, fat mass, glucose, cholesterol, triglycerides and absolute RMR. DNA methylation analysis revealed two differentially methylated CpG sites within ADRB3, and significant global hypomethylation. Postoperatively, ADRB3 methylation correlated positively with RMR, explaining 38% of its variance, alongside with oxygen consumption and carbon dioxide production. Functional analysis supported ADRB3’s role in thermogenesis and lipid metabolism. These findings demonstrate that RYGB not only improves metabolic parameters, but also induces epigenetic remodeling of ADRB3, potentially influencing postoperative energy expenditure. This work provides new insights into the epigenetic regulation of metabolism and highlights ADRB3 as a potential target for personalized obesity treatment in women.