Brain Dopamine Function in Human Obesity

Evidence from neuroimaging studies indicates that aberrant functionality in brain regions that support reward processing and habit formation may be related to an individual's eating behavior and obesity propensity. In particular, our previous research found that increased dopamine D2 receptor binding potential (D2BP) in the dorsal and lateral striatum was positively related to opportunistic eating behaviors, body fat, and body mass index (BMI). However, our findings were contrary to highly-cited previous reports of D2BP correlating with BMI in the opposite direction. The primary aim of this study is to elucidate the reasons for the conflicting results that used somewhat different methodologies. Specifically, our previous study used positron emission tomography (PET) to measure D2BP using the dopamine D2 receptor antagonist radioligand \[18F\]fallypride following a period of dietary stabilization and 3 hours after a standardized breakfast. Reports finding correlations between D2BP and BMI in the opposite direction have typically investigated subjects with higher BMI using the D2 receptor antagonist radioligand \[11C\]raclopride. Furthermore, previous studies were typically conducted in the fasted state, but the subjects' prior food intake was not well-controlled. The present study will attempt to resolve the controversy by measuring D2BP using both \[18F\]fallypride and \[11C\]raclopride in 39 adults, 13 within each of three BMI strata to represent a large BMI range, under controlled overnight fasting conditions following a period of dietary stabilization. The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from \[18F\]fallypride and \[11C\]raclopride.