When does post-ingestive dopamine signaling occur in humans?

The post-ingestive dopamine response is an integral determinant of subsequent eating behavior in animals yet measurement of the post-ingestive response to nutrients in humans has been elusive when assessed in the early post-ingestive period (30 minutes postprandially). We conducted secondary analysis comparing dopamine D2 receptor binding potential (D2BP) measured using [ ¹⁸ F]fallypride positron emission tomography in two inpatient controlled feeding cohorts consuming standardized diet (50% carbohydrate; 35% fat; 15% protein) with similar characteristics and procedures but differing in time since last meal: confirmed overnight fast (n=57; 66.7% female; BMI 29.6±7.6 kg/m ² ; 31.9±7.2 years old) and 2-hours after a standardized meal reflecting 20% of energy requirements (n=43; 48.8% female; BMI 28.8±7.8 kg/m ² , 31.3±7.7 years old). Compared to the fasted cohort, the 2-hour postprandial cohort exhibited significantly reduced whole striatal D2BP (p<0.0001) as well as in clusters in insular cortex, prefrontal cortex which remained after adjustment for age, sex, and insulin sensitivity. Voxelwise comparisons of the relationship between D2BP and BMI in the fasted and fed cohorts reveals clusters within dorsolateral and ventral striatum where dopamine level is dependent on postprandial state and adiposity. Given the similarities between protocol procedures and participant characteristics, our results suggest that the post-ingestive dopamine response to nutrients may be prominent in the extended post-ingestive period and warrant investigation within-subject.