Human obesity is a major public health problem that is driven by a complex combination of behavioral, genetic, environmental, biological and neurobiological factors. Neuroimaging studies in humans find altered dopamine (DA) function and reward-related behavior associated with obesity but conflicting findings limit our understanding of these complex relationships.

The Hershey Lab has received funding from NIH (Central Dopamine Receptors in Obesity, DK085575), to investigate striatal D2 dopamine receptors (D2R; measured with a novel, highly specific D2R PET radioligand [11C]N-methyl)benperidol ([11C]NMB)) in non-diabetic obesity. We found that D2R binding was not related to BMI, but was related to obesogenic eating, reward-related traits and genetic markers of DA signaling across both obese and normal weight subjects. Furthermore, we found that lower glucose-induced pancreatic insulin release in non-diabetic subjects related to altered reward-related traits. Together, these data suggest that dopamine, insulin and reward may be linked in ways that help us understand neurobiological risk for and response to obesity.

Third Slide

Proposed model of interactive factors linking genetics, D2R, insulin resistance and behavior in human obesity. We are continuing to test hypotheses about these proposed relationships.