Brain satiety circuit activated by gastric stimulation

Abstract

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Objectives: Gastric stimulation is a new obesity treatment that leads to decreased food intake and reduced body weight. The neurobiological mechanism underlying the decreased food intake from gastric stimulation is unknown. Here we use the Transcend® Implantable Gastric Stimulator (IGS®) system, which generates electric signals to induce the expansion of the fundus, to assess the effect of gastric stimulation on regional brain activity in obese subjects.

Methods: Six female and 1 male obese subjects (47.8 ±6.3 yrs of age) who had the IGS implanted for 1-2 years were evaluated with PET and FDG, which was used to obtain measures of regional brain metabolism. Brain metabolism was evaluated in food deprived (17-19 hours) subjects during activation (on) and deactivation (off) of the IGS in separate days (> 2 weeks). The absolute metabolic images were analyzed using Statistical Parametric Mapping (SPM; p < 0.005, uncorrected, cluster size > 200 voxels) and regions of interest (ROI; p < 0.05) methods. The Eating Questionnaire-Eating Inventory (TFEQ) was obtained to assess 3 factors that influence food consumption in humans: restraint, disinhibition and hunger components.

Results: SPM analysis of the brain metabolic images showed that during the “on” conditions subjects had significantly higher activity in right orbitofrontal cortex, right frontal cortex, right parahippocampus and anterior cerebellum (p < 0.005) than during the “off” condition. In addition, the ROI analysis showed that during the “on” condition subjects also had higher metabolism in right putamen (p < 0.03) and right ventral striatum (p < 0.04) than during the “off” condition. The TFEQ did not differ significantly between the “on” and the “off” conditions. Correlation analysis revealed that the “disinhibition” factor was significantly associated with the metabolic changes between “on” and “off” in left hippocampus (r = 0.9, p < 0.002).

Conclusions: Activation of the orbitofrontal and right hippocampal, which are regions that contain nuclei involved in the regulation of satiety, and motivation to eat respectively suggest that this is the mechanism by which gastric stimulation decreases food intake. It also suggests that anterior cerebellum, a region that is not typically associated with appetitive behaviors may also be involved with food intake.

Research Support (if any): Supported by DOE (OBER) and NIH/GCRC (5-MO1-RR-10710).