In this issue of Science Translational Medicine, Laferrère and colleagues describe a metabolite profiling approach to investigate changes in the circulating metabolome after equivalent weight loss spurred by either gastric bypass surgery (GBP) or dietary intervention. The results reveal that GBP enhances branched chain amino acid metabolism by mechanisms separate from weight loss. These observations raise the possibility that changes in circulating amino acids play a role in the correction of glycemic control observed shortly after GBP.