Corticostriatal dopamine networks mediate impulsivity in obesity and insulin resistance

Abstract

Obesity and obesity-associated disease together are a leading cause of death worldwide. Recent research demonstrates striking similarities between obesity and addiction in their dysregulation of brain dopamine systems. Insulin functions to modulate dopamine neurotransmission in the striatum and cortex. These areas are critically involved in reward, habits, and cognitive control, suggesting that impaired central insulin signaling may produce functional impairments in systems mediating food acquisition and overconsumption. In this human-subjects study, we demonstrate that impaired insulin signaling is associated with heightened impulsivity and that this is mediated through specific cortico-thalamo-striatal-cortical motor and attention networks. Further, we observed independent associations of visceral adiposity and insulin resistance with impaired striatal dopamine neurotransmission and impulsive behavior, suggesting a specific role for striatal dysregulation in the development and pathogenesis of obesity.