Studies report opposite effects of Roux-en-Y gastric bypass (RYGB) and diet-induced calorie restriction on the metabolic regulator fibroblast growth factor 21 (FGF-21). However, no studies have so far investigated this, using a randomized controlled design in order to examine any potential direct effect of surgery. We, therefore, aimed to test the hypothesis that weight loss induced by RYGB, but not calorie restriction per se, increased fasting and postprandial responses of FGF-21.


Subjects with obesity (BMI: 45.8±4.4 kg/m2) but normal glucose tolerance were randomized to RYGB after 8 (n = 14) or 12 weeks (n = 14) on a low-calorie diet, with those operated at week 12 serving as a ‘pair-fed’ control group for those operated in week 8. Fasting active FGF-21 (1-181) and postprandial responses after a mixed meal were assessed at week 7 and 11. Fasting levels were evaluated with mixed models with a group-week interaction and postprandial responses with repeated measures including a group-week-time interaction. All models were adjusted for age and gender.


Week 0-7 did not lead to any between-group differences in body weight (P=0.87); however, weight loss from week 7-11 was larger in RYGB operated subjects compared to controls (RYGB: 7.7±0.6kg vs. control: 4.9±0.6kg, P<0.01). When compared to the control group, we found no differences in changes in fasting FGF-21 (RYGB: -11.1±23.3pg/ml vs. control: -1.4±23.3pg/ml, P=0.76) or responses to a mixed meal (P=0.28) 3 weeks after RYGB. However, our data do show large interindividual variations in both fasting and postprandial responses.


Our data do not support an acute effect of RYGB on fasting FGF-21 or postprandial responses to a mixed meal when compared to a control group in similar negative energy balance.