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.

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.

We have investigated striatal D2 dopamine receptors in non-diabetic obesity and found that D2R binding 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.