The overall goal of this proposal is to examine the effect of different degrees of insulin resistance on brain reward circuits in obese and normal-weight Hispanic children. Brain reward circuit activity will be determined using functional magnetic resonance imaging (fMRI) in two groups of Hispanic children (aged 8 - 11 years) who provide a large range of insulin resistance. This proposal is a first step in testing the unifying hypothesis that peripheral insulin resistance is not only a consequence of obesity but in turn contributes to positive energy balance through a disruption of central food intake regulation. Furthermore, the research proposal is designed to provide important training to prepare me for an independent and inter-disciplinary research career. Dr. Adam's immediate career goals are to: 1) become an expert in the use of fMRI as well as analyze the collected data to help elucidate the central mechanisms of food intake regulation;2) expand knowledge on mechanisms of food intake regulation, obesity and type 2 diabetes to the pediatric population;3) become competent in research regarding brain anatomy and the different anatomical structures that are involved in reward processing;4) deepen knowledge about the mechanistic relationship between insulin sensitivity and obesity;and, 5) mentor undergraduate and graduate students in preparing them for careers in prevention and treatment of childhood obesity and type 2 diabetes. The overall long-term career goal is to become an independent and inter-disciplinary investigator focused on the understanding of food intake regulation in childhood obesity. The specific training activities associated with this KO1 will involve: 1) direct mentorship from Dr.Michael Goran, Dr. Richard Bergman, Dr. Dianne Lattemann, Dr. Zhong-Lin Lu and Dr. Weigensberg;2) attending seminars and formal classes to be trained in the subject areas and methodological skills necessary to complete the study as well as in career development (eg neuroscience;fMRI methodology;biostatistics;grant writing);and 3) attend conferences to improve scientific expertise, create a professional network and provide exposure to present and discuss study findings.
The proposed study will examine how insulin resistance may not only be a consequence of obesity but also a cause for overeating through a disruption of central food intake regulation. The results will substantiate the importance of insulin sensitivity as a primary target for obesity treatment and early age intervention for successful prevention of obesity.
