Adipose Tissue and Insulin Resistance in Polycystic Ovary Syndrome

描述（由申请人提供）： Sam博士的长期目标是在多囊卵巢综合征（PCOS）领域以患者为导向的研究中追求独立的职业生涯。候选人目前是在伊利诺伊大学医学院内分泌科终身教职的第二年。一个指导病人为导向的研究职业发展奖将促进她的调查技能的增长，并让她获得必要的知识和专业知识，以追求独立的研究。她的导师，西奥多Mazzone博士是美国国立卫生研究院资助的脂肪组织生物学专家和内分泌科科长。 脂肪组织分布和炎症在PCOS中与胰岛素抵抗相关的作用尚不清楚，这将是本研究的重点。我们的假设是，独立于体重指数（BMI），PCOS与1）腹部脂肪分布的改变有关，这有利于内脏和深层皮下脂肪库的增加，并对胰岛素敏感性产生不利影响，2）脂肪组织巨噬细胞浸润增加，脂肪组织中炎症标志物的活化和表达增加，导致炎症和胰岛素抵抗的发展。将研究患有PCOS的育龄妇女和种族、年龄和BMI匹配的生育正常妇女组。这项研究将包括非肥胖以及超重和肥胖组。受试者将在L4-L5水平接受双光子X射线吸收测定法（DEXA）和计算机断层扫描（CT），以确定腹部脂肪分布。将通过频繁采样的静脉葡萄糖耐量试验确定胰岛素敏感性，并将确定炎症标志物的循环水平。将检查脐周区域的皮下脂肪组织的巨噬细胞浸润和巨噬细胞活化标志物以及炎症标志物表达。将获得内脏脂肪，并将在接受减肥手术的病态肥胖受试者亚组的类似研究中进行检查。 公共卫生相关性：PCOS是育龄妇女中最常见的激素异常，并使2型糖尿病的风险增加7倍。到目前为止，这种疾病的病因和导致胰岛素抵抗的异常仍然未知。这项拟议的研究将具有重大的公共卫生意义，并将探索脂肪组织（迄今尚未研究）在PCOS胰岛素抵抗和糖尿病发展中的作用。

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.