Cerebral effects of GLP-1 receptor blockade before and after Roux-en-Y Gastric Bypass in obese women: a proof-of-concept resting-state fMRI study.

AIMS Roux-en-Y Gastric Bypass (RYGB) is an intervention to achieve long term weight loss in obesity. RYGB provokes increases in glucagon-like peptide-1 (GLP-1) production and sensitivity, which have been implicated in RYGB-related changes in brain responses to food cues and food intake. The effects of these RYGB-related changes in GLP-1 on cerebral resting-state functioning are unknown. MATERIALS AND METHODS In 9 middle-aged obese females in the fasted state, we studied the effects of RYGB and GLP-1 on 5 a priori selected networks implicated in food- and reward-related processes as well as environment monitoring (default mode, right frontoparietal, basal ganglia, insula/anterior cingulate, and anterior cingulate/orbitofrontal networks). RESULTS Before surgery, GLP-1 receptor blockade (using exendin9-39), was associated with increased right caudate nucleus (basal ganglia network) and decreased right middle frontal (right frontoparietal network) connectivity compared to placebo. RYGB resulted in decreased right orbitofrontal (insula/anterior cingulate network) connectivity. In the default mode network, after surgery, GLP-1 receptor blockade had a larger effect on connectivity in this region than GLP-1 receptor blockade before RYGB (all PFWE <0.05). Results remained similar after correction for changes in body weight. Default mode and right frontoparietal network connectivity changes were related to changes in BMI and food scores after RYGB. CONCLUSIONS These findings suggest GLP-1 involvement in resting-state networks related to food and reward processes and monitoring of the internal and external environment, pointing to a potential role for GLP-1 induced changes in resting-state connectivity in RYGB-mediated weight loss and appetite control. This article is protected by copyright. All rights reserved.