This project focuses on the identification of early metabolic disturbances implicated in the genesis of juvenile obesity. The investigator propose to determine whether hyperinsulinemia or insulin resistance is the primary defect that is present in """"""""high-risk"""""""" preadolescent children of obese parents compared to low risk lean preadolescent children of nonobese parents prior to the development of obesity. The applicant will use a modification of the hyperglycemic clamp to quantify insulin secretion in the two groups and to independently assess the influence of gut factors on the betas cell response to hyperglycemia; and she will attempt to ascertain the relationship between leptin levels and the hyperinsulinemia of juvenile obesity; as well as assess whether defective catecholamine induced stimulation of lipolysis might contribute to further weight gain in obese children. To address these issues the investigator will utilize isotopic infusions and microdialysis techniques. The observed metabolic defects will be related to alterations in fat distribution assessed by MRI. The long-term goal is to generate data that will lead to the development of new strategies for the prevention and treatment of juvenile obesity.
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