Ectopic Fat, Adipocytokines, and Atherosclerosis in Postmenopausal Women

绝经后女性的异位脂肪、脂肪细胞因子和动脉粥样硬化

• 批准号: 7933825
• 负责人: Rachel P Wildman
• 金额: $ 80.96万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7933825
• 关键词: Address; Adipose tissue; Ancillary Study; Atherosclerosis; Benefits and Risks; Biological Assay; Blood specimen; Body Size; Body mass index; C-reactive protein; Cardiac; Cardiovascular Diseases; Cardiovascular system; Choristoma; Clinical Trials; Clinical Trials Design; Collection; Controlled Clinical Trials; Coronary Arteriosclerosis; Coronary heart disease; Data; Deposition; Development; Enrollment; Epicardium; Estrogen Therapy; Estrogens; Fatty acid glycerol esters; Glucose; Goals; Heart; Heart Rate; Hepatic; High Density Lipoprotein Cholesterol; Hormones; Hypertension; Image; Individual; Insulin; Insulin Resistance; Intervention; Interview; Kidney; Knowledge; Lead; Leptin; Liver; Location; Malnutrition; Measurement; Measures; Menopause; Metabolic; Molecular Weight; Morbidity - disease rate; Myocardium; Non obese; Nutritional status; Obesity; Oral; Overweight; Pancreas; Participant; Pericardial body location; Placebo Control; Placebos; Postmenopause; Prevention; Proteins; Protocols documentation; Randomized; Randomized Controlled Trials; Research; Retinol Binding Proteins; Risk; Risk Factors; Risk Reduction; Scanning; Serum; Specimen; Study Subject; Testing; Thick; Tissues; Triglycerides; Vascular Diseases; Weight; Woman; X-Ray Computed Tomography; adiponectin; base; cardiovascular disorder risk; cardiovascular risk factor; cost; follow-up; hormone therapy; improved; indexing; intima media; novel; pericardial sac; research study; tool; transdermal estrogen; treatment strategy; waist circumference

Individuals of similar body size may differ widely in their risk of cardiovascular disease (CVD), suggesting that factors other than body mass index or total body adiposity are key determinants of adiposity-associated CVD risk. Deposition of triglyceride in lean tissues (ectopic fat) can occur in the liver, heart, muscle, pancreas, and kidneys and is associated with various forms of morbidity, including CVD. The location of the fat may determine its impact on CVD risk. Adipocytokines, hormones released by adipose tissue, appear to be associated with both vascular disease and the deposition of fat in lean tissues, even in non-obese individuals. However, little is known regarding the potentially differential effects of fat in the heart vs. liver on cardiometabolic risk factors, adipocytokine profiles, or atherosclerosis, and their independence from body size or waist girth measures. Additionally, the extent to which menopausal hormone therapy (MHT) may alter adipocytokine and ectopic fat levels is not known. This study proposes to fill these gaps in knowledge by examining the relationships of hepatic and cardiac fat deposition with the progression of atherosclerosis in postmenopausal women. In addition, it will provide novel information concerning the effects of MHT on adiposity, adipocytokines, and ectopic fat. This application takes advantage of participants, specimens, and data from a fully enrolled, ongoing clinical trial of 728 women called the Kronos Early Estrogen Prevention Study (KEEPS). KEEPS is a randomized, placebo-controlled clinical trial examining the effects of MHT given to recently postmenopausal women on atherosclerosis progression. The central hypothesis of this ancillary application is that the location of fat, rather than body size or total adiposity, is an important determinant of cardiometabolic abnormalities and atherosclerosis, and the primary goal of this project is to identify the fat locations which carry the greatest atherogenic potential. The specific aims are: 1.) To examine the crosssectional relationships between fat in different locations (liver, epicardium, pericardium) with cardiometabolic risk factors, adipocytokines, and subclinical atherosclerosis; 2.) To identify the impact of oral and transdermal MHT vs. placebo on ectopic fat measures and adipocytokines, and 3).To examine the longitudinal relationships between fat in different locations with changes in cardiometabolic risk factors, adipocytokines, and subclinical atherosclerosis. The proposed study will generate information which will assist in better stratifying CVD risk in women and lead to improved treatment strategies, including perhaps MHT, to reduce risk in both obese and non-obese women. This, in turn, should lead to targeting of prevention and treatment efforts to those women (lean or obese) with the greatest risk of CVD in a manner tailored to their individual metabolic and adipose tissue profiles.

体型相似的个体患心血管疾病（CVD）的风险可能存在很大差异，这表明除体重指数或全身肥胖以外的其他因素是肥胖相关CVD风险的关键决定因素。甘油三酯在瘦肉组织（异位脂肪）中的沉积可发生在肝脏、心脏、肌肉、胰腺和肾脏，并与包括心血管疾病在内的各种形式的发病率有关。脂肪的位置可能决定其对心血管疾病风险的影响。脂肪细胞因子，由脂肪组织释放的激素，似乎与血管疾病和瘦组织中的脂肪沉积有关，即使在非肥胖个体中也是如此。然而，关于心脏和肝脏脂肪对心脏代谢危险因素、脂肪细胞因子谱或动脉粥样硬化的潜在差异影响，以及它们与体型或腰围的独立性，我们知之甚少。此外，绝经期激素治疗（MHT）可能改变脂肪细胞因子和异位脂肪水平的程度尚不清楚。本研究提出通过检查绝经后妇女肝脏和心脏脂肪沉积与动脉粥样硬化进展的关系来填补这些知识空白。此外，它将为MHT对肥胖、脂肪细胞因子和异位脂肪的影响提供新的信息。该应用程序利用了参与者、样本和数据，这些数据来自一项完全注册的、正在进行的临床试验，名为Kronos早期雌激素预防研究（KEEPS）。KEEPS是一项随机、安慰剂对照的临床试验，旨在研究绝经后妇女服用MHT对动脉粥样硬化进展的影响。这个辅助应用的中心假设是脂肪的位置，而不是身体大小或总脂肪，是心脏代谢异常和动脉粥样硬化的重要决定因素，这个项目的主要目标是确定携带最大动脉粥样硬化潜力的脂肪位置。具体目标是：1)研究不同部位（肝脏、心外膜、心包）脂肪与心脏代谢危险因素、脂肪细胞因子和亚临床动脉粥样硬化之间的横断面关系；2)。2)确定口服和透皮MHT与安慰剂对异位脂肪测量和脂肪细胞因子的影响。研究不同部位脂肪与心脏代谢危险因素、脂肪细胞因子和亚临床动脉粥样硬化之间的纵向关系。拟议的研究将产生有助于更好地划分女性心血管疾病风险的信息，并导致改进的治疗策略，包括可能的MHT，以降低肥胖和非肥胖女性的风险。反过来，这应该导致针对那些心血管疾病风险最大的妇女（瘦或肥胖）的预防和治疗工作，并根据她们的个人代谢和脂肪组织特征进行定制。