Neurobiobehavioral Underpinnings of Intergenerational Obesity - Abstract Maternal obesity is a major public health problem affecting 20 million women in the United States and accounting for 22 to 42% of the prevalence of childhood obesity, a significant public health challenge. Currently, 1 in 8 children aged 2-5 years old have obesity, which is associated with increased risk of obesity and chronic diseases in adulthood. Experimental studies demonstrate that in utero exposure to maternal obesity and high-fat diet can alter fetal development of frontocorticolimbic circuitries that regulate inhibitory control and reward sensivity leading to increased food intake and obesogenic behaviors. However, very little is known about early life neurobiobehavioral mechanisms that may underpin intergenerational obesity in humans. Understanding of neonatal brain and neurobehavioral mechanisms that are linked to modifiable in utero exposures, and that also predict weight outcomes during a sensitive period of obesity development, is urgently needed to inform effective prevention studies. The current proposal aims to address this knowledge gap by leveraging data and biospecimens from a longitudinal pre-birth cohort (5R01MH113883) to examine the following specific aims: 1) Determine associations of pre-pregnancy obesity, diet, and adipocyte-specific inflammation with newborn brain structural and functional connectivity in networks involved in reward processing and inhibitory control; 2) Examine associations of pre-pregnancy obesity, diet, and adipocyte-specific inflammation with self-regulation in infancy; and 3) Determine associations of newborn brain connectivity and infant self-regulation with body mass index trajectories during the first 2 years of life. This will be the first study in humans to use advanced multimodal imaging techniques, prenatal dietary assessments, infant neurobehavior assessments, and longitudinal growth measures, while leveraging maternal adipocyte biology, to comprehensively characterize a neurobiobehavioral model of intergenerational obesity. Through rigorous mentor-directed didactic and hands-on training, coursework, seminars, and career development activities, the candidate will build on her strong research foundation and achieve four training goals: 1) strengthen knowledge on prenatal dietary assessments, 2) acquire new knowledge on the neurobiology of eating behaviors and the MRI modalities used to assess relevant networks, 3) improve understanding of neurobehavioral assessments tools for the evaluation of self-regulation in infancy and toddlerhood, and 4) strengthen skills in causal mediation analyses. By the end of the training period, the candidate will position herself uniquely to achieve her goal of becoming an independent investigator leading an innovative multidisciplinary research program (integrating metabolism, nutritional science, neuroscience, and behavioral science) on the neurocognitive basis of intergenerational obesity. The skillset, knowledge, data, and publication record gained from this proposal will enable the candidate to compete successfully for an R01-funded grant to mechanistically investigate targets for intervention during the first 1000 days, a sensitive period for child obesity development.
