Obese individuals show blunted striatal response to food: Relation moderated by DRD2 gene

Abstract

As dopamine D2 receptor density in the striatum is inversely related to BMI among obese humans and obese rats have lower basal dopamine levels and reduced D2 receptor expression, it has been proposed that people with hypofunctioning reward circuitry overeat to boost a sluggish reward system.We conducted four fMRI studies that tested whether obese humans would show blunted activation of the striatum in response to food. In all studies, obese humans showed reduced activation of the striatum in response to receipt of chocolate milkshake and BMI was inversely related to activation in the striatum. As humans with an A1 allele of the Taq1 A1 DRD2 gene have 30–40% fewer D2 receptors than those without an A1 allele, we next tested whether the relation between obesity and blunted striatal response would be amplified in those with the A1 allele because they have reduced dopamine signaling capacity: the inverse relation of BMI to blunted striatal response to food receipt was amplified in those with the A1 allele. Finally, we tested whether humanswith a blunted striatal response to food intake are at increased risk for futureweight gain andwhether the presence of the A1 allele of the DRD2 gene amplified this relation: the blunted striatal response predict futureweight gain over a 1-year follow-up period, but only for those with the A1 allele. Findings collectively suggest that hypofunctioning food reward circuitry increases risk for obesity. doi:10.1016/j.appet.2008.04.233