This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The prevalence of overweight among children has been on the rise for several decades and is now recognized as a major public health concern in North America. As in adults, hypertension, lipid abnormalities, and asthma are associated with obesity in children. Obesity, diabetes, hypertension, and lipid abnormalities are all risk factors for atherosclerotic cardiovascular disease (CVD), the number 1 killer in adults . Any one of these risk factors raises ones likelihood of developing CVD, but when these risk factors cluster together in an individual the risk of developing CVD escalates. The clustering of these risk factors in an individual is called the metabolic syndrome. The diagnostic criteria for the metabolic syndrome in adults are well defined, while criteria for adolescents are being formulated. The definition of the metabolic syndrome for adults has been adapted for adolescents2 ages 12-21 years. The prevalence of the metabolic syndrome is estimated to be about 24% in adults and 4% in adolescents. This number jumps to 29% in adolescents with >95%ile BMI . Obesity, particularly truncal obesity, is a cardinal sign of the metabolic syndrome. However, not all obese adults or adolescents develop features of the metabolic syndrome. In fact, some remain remarkably metabolically normal in spite of significant obesity. There is likely a genetic basis for this observation. Recent research in diabetes and CVD risk factors in adults has revealed novel insights into their pathophysiology. Adipose tissue, a common feature in many with T2DM and CVD, is now considered a complex metabolic organ. The adipocyte is an active secretory cell releasing what is collectively called 'adipokines,' such as tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), leptin, resistin, and adiponectin. Several studies in lean, obese, insulin resistant, and/or diabetic adults have shown dysregulation in these adipocyte-derived compounds. These abnormalities appear to be predictive of which subjects are likely to develop T2DM and/or CVD. Very little research has been done in children looking at these adipokines and their relationship to obesity and obesity-related conditions. Fewer studies are prospective in design, so the temporal relationship between dysregulated adipocyte metabolism and disease is even less well understood. The purpose of this study is to begin to characterize the adipocyte-derived inflammatory and hormonal contributions to obesity and obesity-related conditions in children. This is an area of great research interest nationally. Our institution needs preliminary data and research experience to be competitive for extramural awards. One purpose of this project is to contribute to this much-needed preliminary work. Funding has been secured from the Dean's/CUMG Research Development Fund for this project, award dates 7/1/2004 - 6/30/2006. The GCRC Resource Request Form and the application include budgetary specifics.
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