PET/fMRI demonstrates that bariatric surgery may reverse striatal dopaminergic dysfunction in women with obesity

Abstract

Background: Central mechanisms may play a role in the success of bariatric surgery (BS), the treatment of choice for refractory obesity. We hypothesize that central dopaminergic receptor function in striatal brain regions is a pivotal mechanism in the success of BS. Methods: We conducted a cross-sectional study to investigate central dopamine type 2 and 3 receptors (D2/3 R) within striatal brain regions in successful weight loss (WL) through BS. Positron Emission Tomography was used to map nondisplaceable binding potential (BPND) of D2/3 R in 48 women: 19 successful responders to BS, 12 with obesity (OB), and 17 normal-weight controls. Parametric maps were compared between-groups in regions of interest and at voxel-level. We also investigated brain blood oxygenation level-dependent (BOLD) responses to food content using functional Magnetic Resonance Imaging (fMRI) and how key variables correlate with D2/3 R binding. Results: We find mean D2/3 R BPND significant differences between OB and controls in the ventral striatum (p = 0.042) and at voxel-level across striatum between OB and the other groups (p < 0.05). Food content (Food > Non-food, p = 0.05) reveals significantly higher neural activation in striatum also for OB compared to the other groups. Moreover, D2/3 R BPND values correlate with dysfunctional self-report measures of eating behaviors, incentive salience to food cue and high-calorie food preferences in obesity. Notably, BOLD responses (Food > Baseline) in striatum correlate positively with D2/3 R binding in ventral striatum. Conclusions: Striatal dopaminergic dysfunction in obesity may enhance salience to food cues, driving cravings and compulsive eating. BS may reverse the striatal molecular and functional disruptions found in obesity.