Nicole L. Mihalopoulos, MD, MPH is an Assistant Professor in the Department of Pediatrics at the University of Utah. The purpose of this Mentored Patient-Oriented Career Development Award is to provide Dr. Mihalopoulos with a structured Career Development Program and a mentored research plan that will enable her to become an independent clinical researcher in the field of preventive cardiology. Dr. Mihalopoulos'specific interest is in the field of adolescent obesity and adipokines, specifically how differing levels of adipokines may protect some obese individuals from developing metabolic dysfunction. This K23 award investigates why some obese children, adolescents and adults exhibit evidence of metabolic dysfunction (dyslipidemia, insulin resistance, hypertension) and some do not. Specifically, she will study how adiponectin and leptin, two adipokines that affect insulin resistance and lipid metabolism, and brown adipose tissue (BAT) activity influence this variation. She will expand her knowledge and skill in this area with the following specific aims.
Specific Aim 1 will evaluate the relationship between BAT, the adiponectin/leptin (A/L) ratio, and metabolic dysfunction in children, adolescents, and adults.
This aim i ncludes two crosssectional studies. In study 1A, BAT activity, A/L ratios and metabolic measures will be determined in 600 subjects (8-99yo) who are undergoing a clinically indicated positron emission tomography with computed tomography (PET/CT). In study 1B similar measures, including a PET/CT, will be performed on 60 obese, but otherwise healthy, older adolescents/young adults (18-30yo) recruited from Dr. Mihalopoulos'Adolescent Preventive Cardiology Clinic and Dr. Steven C. Hunt's cardiovascular genetics extremely obese cohorts. These two studies will evaluate possible correlations between BAT activity, A/L ratio and metabolic dysfunction.
Specific Aim 2 will determine whether serum concentrations of adiponectin and leptin are associated with metabolic dysfunction during puberty among obese and normal weight children and adolescents.
This aim i ncludes two longitudinal studies. Study 2A is a longitudinal cohort of 642 primarily normal weight black and white children and adolescents from Project HeartBeat! (PHB) established by Dr. Darwin R. Labarthe. PHB was unique because it followed children every 4 months for four years (1991-1995) to assess changes in lipids and anthropometry during puberty. In study 2B, 220 obese children and adolescents (8-18yo) recruited from Dr. Mihalopoulos'Adolescent Preventive Cardiology Clinic and Dr. Steven C. Hunt's cardiovascular genetics extremely obese cohorts will have annual determinations of adiponectin and leptin for as long as 4 years. Study 2B will provide data describing how the A/L ratio changes during puberty in obese children and adolescents. This proposal takes advantage of expertise in pediatric cardiology, intermediary metabolism of adipose tissue, positron emission tomography, cardiovascular disease genetics, pediatric endocrinology, genetic epidemiology and multi-level statistical modeling found within the University of Utah. Dr. Mihalopoulos has also identified experts in brown adipose tissue metabolism and preventive cardiology to serve as advisors. Completion of the four studies will provide a much better understanding of whether variations in BAT and the A/L ratio are responsible for variations in cardiovascular disease risk among the obese. Determining the factors that appear to provide protection for some obese youth and adults from developing metabolic dysfunction will enable Dr. Mihalopoulos to pursue future studies of strategies to reduce the risk of cardiovascular disease risk. At the completion of the training program, Dr. Mihalopoulos will be poised to be an independent investigator in the field of preventive cardiology with experience in study design, laboratory skills, positron emission tomography and statistical techniques.

Public Health Relevance

This proposal has both clinical and public health significance because little is known about the metabolic function and significance of adipose tissue during puberty. This study will increase our understanding of the role of adipose tissue before, during, and after puberty and may lead to early identification of risk factors and intervention to prevent cardiovascular disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (F1))
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Scott, Jane
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University of Utah
Schools of Medicine
Salt Lake City
United States
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Mihalopoulos, Nicole L; Urban, Brittney M; Metos, Julie M et al. (2017) Breast-feeding, Leptin:Adiponectin Ratio, and Metabolic Dysfunction in Adolescents with Obesity. South Med J 110:347-352
Society for Adolescent Health and Medicine (2016) Preventing and Treating Adolescent Obesity: A Position Paper of the Society for Adolescent Health and Medicine. J Adolesc Health 59:602-606
Eissa, Mona A; Mihalopoulos, Nicole L; Holubkov, Richard et al. (2016) Changes in Fasting Lipids during Puberty. J Pediatr 170:199-205
Tak, Casey R; Yu, Tian; Sherwin, Catherine M T et al. (2016) Optimizing enrollment in pediatric obese patients: reflections on recruitment characteristics. Int J Adolesc Med Health 29:
Mihalopoulos, Nicole L; Spigarelli, Michael G (2015) Comanagement of Pediatric Depression and Obesity: A Clear Need for Evidence. Clin Ther 37:1933-7
Grimsrud, Kristin N; Sherwin, Catherine M T; Constance, Jonathan E et al. (2015) Special population considerations and regulatory affairs for clinical research. Clin Res Regul Aff 32:47-56
King, Marta A; Nkoy, Flory L; Maloney, Christopher G et al. (2015) Physicians and Physician Trainees Rarely Identify or Address Overweight/Obesity in Hospitalized Children. J Pediatr 167:816-820.e1
Long, Katelyn N G; Long, Paul M; Pinto, Snehal et al. (2013) Development and validation of the Indian Adolescent Health Questionnaire. J Trop Pediatr 59:231-42
Mihalopoulos, Nicole L; Phillips, Terry M; Slater, Hillarie et al. (2011) Validity and reliability of perinatal biomarkers of adiposity after storage as dried blood spots on paper. Am J Hum Biol 23:717-9
Mihalopoulos, Nicole L; Holubkov, Richard; Young, Paul et al. (2010) Expected changes in clinical measures of adiposity during puberty. J Adolesc Health 47:360-6