The Role of Gut-Brain Pathways on Childhood Obesity and Type 2 Diabetes Development - PROJECT SUMMARY/ABSTRACT Childhood obesity and youth-onset type 2 diabetes (T2D) are increasing at an alarming rate, yet the underlying mechanisms remain poorly understood. Gut-derived hormones, including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), and ghrelin, play a crucial role in gut- brain communication, regulating appetite and glucose metabolism. Disruptions in these pathways during childhood and adolescence may contribute to heightened obesity and T2D risk. This study will investigate how gut hormone secretion and neural appetite regulation interact across development and how prenatal exposures and lifestyle factors influence these processes. Maternal gestational diabetes mellitus (GDM) and obesity are well-established risk factors for obesity and T2D in offspring. Our prior work in the BrainChild Cohort has identified neural alterations in children exposed to maternal GDM or obesity, including changes in appetite-regulating brain regions linked to increased energy intake and weight gain. Preliminary data suggest that maternal GDM/obesity exposure is associated with reduced GLP-1 and PYY secretion and diminished ghrelin suppression, potentially impairing satiety signaling and increasing metabolic risk. Leveraging the ongoing BrainChild Longitudinal Cohort, this study will integrate neuroimaging, gut hormone measures, metabolic profiling, and lifestyle assessments (diet, physical activity, sleep) collected longitudinally in children ages 7 to 16 years. We will address three key objectives: (1) determine the relationship between gut hormone secretion, neural appetite regulation, and metabolic outcomes; (2) assess the effects of prenatal GDM/obesity exposure on gut-brain signaling and metabolic risk; and (3) examine how modifiable lifestyle factors influence gut hormone secretion, brain function, and metabolic outcomes. The overarching goal is to test the hypothesis that alterations in gut hormone secretion and hormone-brain interactions from childhood through adolescence increase obesity and T2D risk in youth. Identifying the role of lifestyle factors in these processes will provide a foundation for targeted interventions to prevent obesity and T2D at a critical developmental stage.
