Resveratrol Alleviates High-Fat Diet–induced Obesity and Is Associated with Activation of β3-AR/AMPKα-Related Thermogenic Signaling

Resveratrol (RSV) is a plant-derived polyphenol that has attracted attention for its potential antiobesity effects. However, the molecular mechanisms underlying its metabolic regulation remain unclear. In this study, an integrated network pharmacology analysis was combined with in vivo experiments to investigate the potential mechanisms associated with RSV-mediated metabolic improvement in high-fat diet (HFD)-induced obesity. The network pharmacology analysis suggested that RSV targets pathways related to lipid metabolism and energy homeostasis. In HFD-fed mice, RSV supplementation reduced body weight gain, improved glucose tolerance and lipid profiles, and suppressed adipose inflammation. RSV treatment was also associated with increased β3-AR, phosphorylated AMPKα, and UCP1 expression and was accompanied by corresponding changes in markers associated with lipolysis, fatty acid oxidation, and adipose thermogenesis. These results suggest that the antiobesity effects of RSV may be associated with β3-AR/AMPKα-related thermogenic signaling modulation, supporting its potential application as a food-derived bioactive compound for functional food development.