2018 — 2021 |
Luo, Shan |
K01Activity Code Description: For support of a scientist, committed to research, in need of both advanced research training and additional experience. |
Neural Mechanisms of Overeating Among Children Exposed to Gestational Diabetes Mellitus in Utero @ University of Southern California
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 goal of this study is to test the hypothesis that in utero exposure to GDM leads to abnormal development of brain pathways that regulate eating behavior, which in turn increases food intake and risk for obesity in children. To accomplish this goal, the applicant and her team plan to 1) examine effects of GDM on food intake; 2) associations of GDM exposure with structural and functional connections between brain appetite and reward pathways; 3) explore whether changes in brain circuitry involved in feeding behavior would mediate the link between GDM exposure and increased food intake thus increasing risk for obesity. This will be the first study in humans to use multi-modal imaging techniques to examine neural mechanisms of the link between GDM exposure and obesity risk. Through extensive mentor-directed training, course work and workshops, manuscript and grant writings, scientific presentations at national conferences, the candidate will achieve three training goals 1) strengthen knowledge about GDM physiology, pediatric obesity and nutrition in children (co-mentor Dr. Kathleen Page); 2) build skills in multi-modal imaging, and learn computational methods (e.g., psychological-physiological-interaction, independent component analysis, DTI fiber tracking, graph theory) to analyze functional and structural connectivity data under supervision of Drs. Paul Thompson (primary mentor) and Neda Jahanshad (co-mentor); 3) strengthen skills in advanced statistical modeling (e.g., mediation analysis) (co-mentor Dr. Anny Xiang). By the end of the proposed training period, the candidate will be positioned uniquely as a leader in investigating neural mechanisms for obesity risk in children exposed to maternal diabetes in utero with skills from various disciplines, and compete for an independent R01 application. Furthermore, this proposed project will help the candidate progress towards achieving her long-term career goal, which is to become an independent and innovative research scientist dedicated to investigating underlying mechanisms of obesity from a joint perspective of neuroscience, psychology and endocrinology.
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2021 |
Luo, Shan |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Brain Inhibition Control and Child Obesity Risk @ University of Southern California
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.
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