Project Summary Childhood obesity rate has been increasing dramatically, at great cost for health care and wellbeing. It is highly likely that obesity will persist into adulthood; thus, identifying risk factors contributing to childhood obesity is extremely critical so that prevention strategies can be taken early to reduce the obesity rate. Research suggests that children who were exposed to gestational diabetes mellitus (GDM) in utero have increased propensity of developing obesity. However, there are few human studies aimed to understand the mechanisms explaining this relationship. The primary goal of the applicant’s K01 project was to investigate associations between GDM exposure and brain pathways implicated in appetite regulation, particularly metabolic and reward pathways. The overall goal of this R03 project is to extend findings from the applicant’s ongoing K01 study to test a hypothesis that in utero exposure to GDM may disrupt the prefrontal inhibition control circuitry, resulting in overeating and obesity. To accomplish this goal, the applicant and her team plan to leverage brain and adiposity data available through the Adolescent Brain Cognitive Development (ABCD) study, and 1) investigate relationships between GDM exposure and functional/structural correlates of inhibition control; and 2) use brain-based markers to predict changes in adiposity. This will be the largest study in humans to use multi-modal imaging techniques to examine neural mechanisms of the link between GDM exposure and obesity risk. The proposed study is an extension of the applicant’s K01 project, together by which will allow the candidate to have a comprehensive assessment of brain circuitry involved in appetite regulation and establish a brain-based working model explaining increased obesity risk among children exposed to GDM in utero.