Adipose Tissue and Insulin Resistance in Polycystic Ovary Syndrome

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DESCRIPTION (provided by applicant): The candidate, Dr. Sam, has the long-term goal of pursuing an independent career in patient-oriented research in the field of polycystic ovary syndrome (PCOS). The candidate is currently in the second year of a tenure track faculty appointment in the Section of Endocrinology at University of Illinois Medical School. A Mentored Patient-Oriented Research Career Development Award will facilitate the growth of her investigative skills and allow her to acquire the necessary knowledge and expertise to pursue independent research. Her mentor, Dr. Theodore Mazzone is an NIH funded expert on adipose tissue biology and Division head in the Section of Endocrinology. The role of adipose tissue distribution and inflammation as it relates to insulin resistance in PCOS is unclear and will be the focus of this proposed research. Our hypothesis is that independent of body mass index (BMI), PCOS is associated with 1) alterations in abdominal fat distribution that favor increases in visceral and deep subcutaneous fat depots and adversely impact insulin sensitivity and 2) increases in adipose tissue macrophage infiltration and activation and expression of inflammatory markers in adipose tissue that result in inflammation and development of insulin resistance. Reproductive age women with PCOS and an ethnicity, age and BMI matched group of reproductively normal women will be studied. The study will include non-obese as well overweight and obese groups. Subjects will undergo dual photon x-ray absorptiometry (DEXA) and computerized tomography (CT) at the level of L4-L5 to determine abdominal fat distribution. Insulin sensitivity will be determined from frequently sampled intravenous glucose tolerance test and circulating levels of inflammatory markers will be determined. Subcutaneous adipose tissue from the periumbilical area will be examined for macrophage infiltration and markers of macrophage activation as well as expression of inflammatory markers. Visceral fat will be obtained and will be examined for similar studies in a subset of morbidly obese subjects who undergo bariatric surgery. PUBLIC HEALTH RELEVANCE: PCOS is the most common hormonal abnormality in reproductive age women and increases the risk for type 2 diabetes by 7-fold. To date, the etiology of the disorder and the abnormalities leading to insulin resistance remain unknown. The proposed research will have substantial public health importance and will explore the role of fat tissue (so far not studied) in the development of insulin resistance and diabetes in PCOS.