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

女性的性类固醇、睡眠、体脂肪和血浆甘油三酯

• 批准号: 8326136
• 负责人: DAVID A EHRMANN
• 金额: $ 34.85万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8326136
• 关键词: Adverse effects; Affect; Apolipoprotein E; Apolipoproteins C; Body fat; Cardiovascular Diseases; Characteristics; Chronic; Dexamethasone; Dose; Functional disorder; Glucocorticoids; Goals; Gonadal Steroid Hormones; Hepatic; Homeostasis; Hormonal; Hydrocortisone; Intervention; Kinetics; Lead; Measures; Metabolic; Metabolic Clearance Rate; Metyrapone; Obesity; Obstructive Sleep Apnea; Oligonucleotides; Ovary; Ovulation; Plasma; Prevalence; Principal Investigator; Progesterone; Risk Factors; Sleep; Sleep Apnea Syndromes; Syndrome; Testing; Testosterone; Transdermal substance administration; Triglyceride Metabolism; Triglycerides; Very low density lipoprotein; Woman; apolipoprotein B-100; effective therapy; hypercortisolemia; inhibitor/antagonist; programs; treatment strategy; very low density lipoprotein triglyceride

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.

血浆甘油三酯 (TG) 浓度升高是代谢异常的常见特征 与肥胖有关，也是心血管疾病的主要危险因素。肥胖是主要危险因素 两种疾病在女性中的患病率似乎在增加：多囊卵巢综合征 (PCOS) 和睡眠呼吸紊乱。 PCOS 影响 5-8% 的女性。睡眠呼吸障碍影响最多 10%的女性。阻塞性睡眠呼吸暂停 (OSA) 是睡眠呼吸障碍的最常见原因 在患有 PCOS 的肥胖女性中尤其常见（约 50%）。 PCOS 和 OSA 都会增加这种增加 与肥胖相关的血浆TG浓度，以及PCOS和OSA对血浆TG的影响 浓度似乎是累加的。造成 PCOS 不良影响的机制和 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 患有 PCOS 的肥胖女性血浆 TG 浓度升高的机制 OSA。我们的一般假设是，荷尔蒙环境的改变是 PCOS 的特征 （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， 导致患有 PCOS 和 OSA 的肥胖女性血浆 TG 浓度升高。 此外，我们假设 PCOS 和 OSA 所特有的荷尔蒙异常是 与瘦女性相比，对肥胖女性尤其有害。为了检验我们的假设，我们将测量 肝脏 VLDL-TG 和 VLDL-apoB-100 分泌率、VLDL-TG 血浆清除率以及影响因素 可能会影响 VLDL-TG 血浆清除率（即 VLDL-apoC-ll、VLDL-apoC-III、VLDL- apoE）在四组受试者中：i）患有 OSA（但不包括 PCOS）的肥胖女性； ii) 患有多囊卵巢综合症的肥胖女性 （但不是 OSA）； iii) 没有 PCOS 或 OSA 的肥胖女性； iv) 没有 PCOS 或 OSA 的瘦女性 改变血浆睾酮、孕酮和糖皮质激素的干预措施前后 可用性。更好地了解负责血浆 TG 稳态的机制可能会导致 为患有 OSA 和 PCOS 的女性提供更有效的治疗策略。