We aimed to determine the short- and long-term effects of Roux-en-Y gastric bypass (RYGB) on intact plasma FGF21 levels and to test the hypothesis that RYGB, but not diet-induced weight loss, increases fasting and postprandial responses of FGF21.<h4>Method</h4>Twenty-eight participants with obesity followed a low-calorie diet for 11 weeks. This evidence concerns the gene FGF21 and obesity due to melanocortin 4 receptor deficiency.