Sex steroids, Sleep, Body Fat, and Plasma Triglycerides in Women

血浆甘油三酯(TG)浓度升高是代谢异常的共同特征 与肥胖有关，也是心血管疾病的主要风险因素。肥胖是一个主要的危险因素。 女性患病率似乎增加的两种情况：多囊卵巢综合征(PCOS) 睡眠呼吸紊乱。多囊卵巢综合征影响5%-8%的女性。睡眠呼吸障碍影响高达 10%的女性。阻塞性睡眠呼吸暂停(OSA)是导致睡眠呼吸紊乱的最常见原因 尤其是在患有多囊卵巢综合征的肥胖女性中(~50%)。PCOS和OSA都扩大了增长 肥胖与血浆甘油三酯浓度的关系及PCOS和OSA对血浆甘油三酯的影响 浓度似乎是相加的。造成多囊卵巢综合征不良反应的机制和 OSA对血浆TG代谢的影响尚不清楚。因此，该项目的主要目标是确定 肥胖女性多囊卵巢综合征患者血浆甘油三酯浓度升高的机制 奥萨。我们的普遍假设是多囊卵巢综合征所特有的激素环境的改变 (高雄激素血症和黄体酮缺乏症)和OSA(高皮质醇血症)至少部分是， 导致肥胖女性多囊卵巢综合征和阻塞性睡眠呼吸暂停综合征患者血浆甘油三酯浓度升高。 此外，我们假设，多囊卵巢综合征和阻塞性睡眠呼吸暂停综合征的激素异常是 与瘦、瘦的女性相比，肥胖尤其有害。为了检验我们的假设，我们将测量 肝脏极低密度脂蛋白-甘油三酯和极低密度脂蛋白-载脂蛋白B-100分泌率、极低密度脂蛋白-甘油三酯血浆清除率及其影响因素 可能影响极低密度脂蛋白-甘油三酯的血浆清除(即极低密度脂蛋白-载脂蛋白C-11、极低密度脂蛋白-载脂蛋白C-11、极低密度脂蛋白- APOE)在四组受试者中：一)患有阻塞性睡眠呼吸暂停综合征(但不是多囊卵巢综合征)的肥胖妇女；二)患有多囊卵巢综合征的肥胖妇女 (但不是OSA)；三)没有多囊卵巢综合征或OSA的肥胖女性；以及四)没有多囊卵巢综合征或OSA的苗条女性，两者都是 干预前后会改变血浆睾酮、孕酮和糖皮质激素 可用性。更好地了解血浆甘油三酯稳态的机制可能会导致 对患有阻塞性睡眠呼吸暂停综合征和多囊卵巢综合征的妇女采取更有效的治疗策略。

Increased plasma triglyceride (TG) concentration is a common feature of the metabolic abnormalities associated with obesity and a major risk factor for cardiovascular disease. Obesity is a major risk factor for two conditions that appear to be increasing in prevalence in women: the polycycstic ovary syndrome (PCOS) and sleep disordered breathing. PCOS affects 5-8% of women. Sleep disordered breathing affects up to 10% of women. Obstructive sleep apnea (OSA) is the most common cause for sleep disordered breathing and particularly prevalent in obese women with PCOS (~50%). Both PCOS and OSA augment the increase in plasma TG concentration associated with obesity, and the effects of PCOS and OSA on plasma TG concentration appear to be additive. The mechanisms responsible for the adverse effects of PCOS and OSA on plasma TG metabolism are not known. The primary goal of this project, therefore, is to determine the mechanisms responsible for the increase in plasma TG concentration in obese women with PCOS and OSA. It is our general hypothesis that alterations in the hormonal milieu that are characteristic of PCOS (hyperandrogenemia and progesterone deficiency) and OSA (hypercortisolemia) are, at least in part, responsible for the increase in plasma TG concentration in obese women with PCOS and OSA. Furthermore, we hypothesize that the hormonal aberrations, characteristic of PCOS and OSA, are particularly harmful to obese, compared with lean, women. To test our hypotheses, we will measure the rates of hepatic VLDL-TG and VLDL-apoB-100 secretion, VLDL-TG plasma clearance rate, and factors that may affect VLDL-TG plasma clearance (i.e., the concentrations of VLDL-apoC-ll, VLDL-apoC-lll, VLDL- apoE) in four groups of subjects: i) obese women with OSA (butnot PCOS); ii) obese women with PCOS (but not OSA); iii)obese women without PCOS or OSA; and iv) lean women without PCOS or OSA, both before and after interventions that will alter plasma testosterone, progesterone, and glucocorticoid availability. A better understanding of the mechanisms responsible for plasma TG homeostasis could lead to more effective treatment strategies for women with OSA and PCOS.