description): Dr. Caprio's main Patient-oriented Research (POR) focuses on the identification of early metabolic disturbances implicated in the genesis of juvenile obesity. The studies proposed here are a natural extension of her previous work in this area. She will continue to determine whether hyperinsulmemia or insulin resistance is the primary defect that is present in """"""""high-risk"""""""" lean children of obese parents compared to """"""""low-risk"""""""" lean children of nonobese parents. Both groups of preadolescents will be followed into adolescence to determine the evolution of putative defects in insulin secretion and action. In addition, she plans to determine if increased intramyocellular lipid stores (IMCL) of the soleus muscle are linked to the insulin resistance of childhood obesity and whether defective catecholamine-induces stimulation of lipolysis might contribute to further weight gain in obese children. 1H-NMR spectroscopy will be used to non-invasiveley assess IMCL stores and microdialysis technique to perfuse the subcutaneous adipose tissue with specific Beta1 and Beta2 andrenoceptor agonists, while simultaneously sampling interstitial glycerol concentrations in obese and nonobese children. Given her longstanding interest in studying hormonal and metabolic changes associated with the onset of puberty, she is determining changes in leptin levels in relation to changes in body composition, energy expenditure, LH, FSH, and sex steroids in a cohort of pubertal girls followed throughout puberty. Future directions in POR include: 1) measurement of ATP synthesis in skeletal muscle of obese subjects with known mutation in uncoupling protein 3 (UCP3) by 31P-NMR spectroscopy; 2) metabolic studies to determine the pathogenesis of type 2 diabetes in children and 3) pharmacological treatment of type 2 diabetes in youth use of Pioglitazone to reverse or improve insulin resistance. The K24 aware will not only assist her in her research endeavors, but will allow her to continue to mentor new clinical-scientists in POR. In summary, the combination of the glucose clamping tracer techniques, NMR imaging and for the first time microdialysis and NMR spectroscopy, in these studies will provide the unique opportunity to advance the understanding of the underlying pathophysiology of juvenile obesity. 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 and Type 2 diabetes in children.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Grave, Gilman D
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Yale University
Schools of Medicine
New Haven
United States
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Galderisi, Alfonso; Giannini, Cosimo; Weiss, Ram et al. (2018) Trajectories of changes in glucose tolerance in a multiethnic cohort of obese youths: an observational prospective analysis. Lancet Child Adolesc Health 2:726-735
Tricò, Domenico; Natali, Andrea; Mari, Andrea et al. (2018) Triglyceride-rich very low-density lipoproteins (VLDL) are independently associated with insulin secretion in a multiethnic cohort of adolescents. Diabetes Obes Metab 20:2905-2910
Caprio, Sonia; Perry, Rachel; Kursawe, Romy (2017) Adolescent Obesity and Insulin Resistance: Roles of Ectopic Fat Accumulation and Adipose Inflammation. Gastroenterology 152:1638-1646
Tricò, Domenico; Prinsen, Hetty; Giannini, Cosimo et al. (2017) Elevated ?-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents. J Clin Endocrinol Metab 102:2473-2481
Kursawe, Romy; Dixit, Vishwa D; Scherer, Philipp E et al. (2016) A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents. Diabetes 65:610-8
Van Name, Michelle; Giannini, Cosimo; Santoro, Nicola et al. (2015) Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance. Obesity (Silver Spring) 23:653-61
Santoro, Nicola; Caprio, Sonia; Giannini, Cosimo et al. (2014) Oxidized fatty acids: A potential pathogenic link between fatty liver and type 2 diabetes in obese adolescents? Antioxid Redox Signal 20:383-9
D'Adamo, Ebe; Santoro, Nicola; Caprio, Sonia (2013) Metabolic syndrome in pediatrics: old concepts revised, new concepts discussed. Curr Probl Pediatr Adolesc Health Care 43:114-23
Kim, Grace; Giannini, Cosimo; Pierpont, Bridget et al. (2013) Longitudinal effects of MRI-measured hepatic steatosis on biomarkers of glucose homeostasis and hepatic apoptosis in obese youth. Diabetes Care 36:130-6
Giannini, Cosimo; Feldstein, Ariel E; Santoro, Nicola et al. (2013) Circulating levels of FGF-21 in obese youth: associations with liver fat content and markers of liver damage. J Clin Endocrinol Metab 98:2993-3000

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