DESCRIPTION (provided by applicant): Dr. Renata Belfort De Aguiar is an Instructor in the Department of Internal Medicine, Section of Endocrinology, at Yale University with an interest in translational clinical research at the interface between metabolism and neuroscience. Dr. Belfort De Aguiar is particularly interested in the pathogenesis of diabetes and obesity. During her research fellowship in the laboratory of Dr. Ralph DeFronzo in San Antonio, Texas, she was introduced to techniques used in human studies to measure insulin resistance, including the hyperinsulinemic euglycemic clamp, and the use of glucose tracers to evaluate glucose metabolism. Subsequently, during her clinical fellowship in endocrinology at Yale University, she joined the laboratory of Dr. Robert Sherwin and got involved in studies looking at the influence of blood glucose levels on brain function. The research protocols she has worked under Dr. Sherwin's supervision, involved the use of the insulin clamp technique, eating behavior questionnaires (modified from the addiction research field), and measurement of brain activation by combining visual cues and functional Magnetic Resonance Imaging (fMRI). For the execution of these research projects, Dr. Belfort De Aguiar has collaborated with Professor Todd Constable from the Magnetic Resonance Research Center (MRRC) and Professor Rajita Sinha from the Yale Stress Center. With the use of the techniques described above, Dr. Belfort De Aguiar plans to study normal weight, obese, and patients with type 2 diabetes (T2DM) during high, normal and low blood glucose levels. Brain activation will be measured with fMRI while seeing visual cues (food and non-food pictures). Dr. Belfort De Aguiar also plans to evaluate how weight loss diet will affect brain activation in T2DM subjects. This protocol will help Dr. Belfort De Aguiar to understand the importance of peripheral glucose levels on food behavior, which may be relevant for development of strategies in the treatment of obesity and T2DM. The expertise attained from her research and clinical fellowships have provided the necessary knowledge to develop the proposed project, but further training in behavioral and neuroimaging will be fundamental to Dr. Belfort De Aguiar to become an independent physician scientist in this field. Dr. Belfort De Aguiar is planning to attend courses offered at the MRRC, Yale Stress Center and Yale Clinical Center Investigation to help her gain further expertise in brain metabolism and function including: a) use of brain imaging techniques (fMRI, MRI spectroscopy and positron emission tomography - all available at Yale University); and b) behavioral measurements (visual cues with fMRI, questionnaires). Dr. Belfort De Aguiar will also benefit of the collaboration with the CTSA-funded Yale Center for Analytical Sciences to assist with the collection and analysis of the data. This specific project will give her experience with writing papers and presenting the results at scientific meetings, which will contribute to her academic development, and facilitate her transition to a fully independent clinical investigator. If granted this award, Dr. Belfort De Aguiar will be able to achieve her long term career goal of becoming a clinical translational scientist in the field of neuroscience/metabolism.

PUBLIC HEALTH RELEVANCE: Obesity is one of the leading preventable causes of death in the United States and one of major risk factors for type 2 diabetes. However, the mechanisms driving inappropriate food consumption and the failure to successfully implement diet remain poorly understood. This research looks into the influence of changes in circulating blood glucose on the activation of brain reward-motivation regions associated with the desire for and intake of high calorie foods in obese patients with type 2 diabetes.