Using a 24-week high-AGE diet murine model, we integrate metabolomics, molecular profiling, and functional assays to identify Myr’s efficacy in reversing obesity and metabolic disorders and elucidate the AMPK-PGC1α-UCP1 cascade as the central mechanism driving these benefits. Here, PPARGC1A is linked to obesity due to melanocortin 4 receptor deficiency.