Using a rat model of moderate obesity and insulin resistance and a cell model of hepatocyte steatosis, we report up-regulation of adiponectin, Sirt6, peroxisome proliferator-activated receptor gamma coactivtor-1-α (Ppargc1a/PGC1-α) and forkhead box O1 (Foxo1), as well as increases in both LKB1 and AMPK activities upon RGZ treatment. Here, PPARGC1A is linked to obesity due to melanocortin 4 receptor deficiency.