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.

血浆甘油三酸酯（TG）浓度增加是代谢异常的常见特征 与肥胖和心血管疾病的主要危险因素有关。肥胖是主要危险因素 女性的患病率似乎增加了两种：多囊卵巢综合征（PCOS） 和睡眠不足的呼吸。 PCO会影响5-8％的女性。睡眠失调的呼吸影响到 10％的女性。阻塞性睡眠呼吸暂停（OSA）是呼吸失调的最常见原因 在PCOS的肥胖女性中尤其普遍（约50％）。 PCOS和OSA都增加了增加 在与肥胖相关的血浆TG浓度以及PCOS和OSA对等离子体TG的影响 浓度似乎是加性的。负责PCOS和PCOS不利影响的机制 OSA在等离子体TG代谢上尚不清楚。因此，该项目的主要目标是确定 负责PCOS肥胖女性血浆TG浓度增加的机制和 OSA。我们的总体假设是，PCOS的荷尔蒙环境中的改变 （高雄激素血症和孕酮缺乏症）和OSA（高皮质血症）至少部分是 负责PCOS和OSA肥胖女性血浆TG浓度的增加。 此外，我们假设PCOS和OSA的特征的激素畸变是 与精益妇女相比，对肥胖特别有害。为了检验我们的假设，我们将衡量 肝VLDL-TG和VLDL-APOB-100分泌的率，VLDL-TG血浆清除率以及这些因素 可能会影响VLDL-TG血浆清除率（即VLDL-APOC-LL，VLDL-APOC-LLL，VLDL-的浓度 apoe）在四组受试者中：i）肥胖女性患有OSA（丁克斯）； ii）PCOS的肥胖女性 （但不是OSA）； iii）没有PCOS或OSA的肥胖妇女； iv）没有PCOS或OSA的精益女性，两者都 干预前后会改变血浆睾丸激素，孕酮和糖皮质激素 可用性。更好地理解负责血浆TG稳态的机制可能导致 OSA和PCOS女性的更有效的治疗策略。