MENOPAUSE, GENES AND METABOLISM AFTER WEIGHT LOSS AND EXERCISE

减肥和运动后的更年期、基因和代谢

• 批准号: 7376963
• 负责人: ALICE S. RYAN
• 金额: $ 11.29万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376963
• 关键词: MENOPAUSE; GENES; METABOLISM; AFTER; WEIGHT

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The prevalence of obesity continues to rise in the U.S. with estimates that 1/3 of the population is overweight. The incidence of obesity is 49% in African-American women compared to 33% in Caucasian women. Moreover, African-American women are significantly more insulin resistant and have twice the prevalence of type 2 diabetes than Caucasians. The reasons for these racial disparities are not entirely explained by differences in obesity. The hypotheses are that there are ethnic (African American vs. Caucasian) and genetic differences in the mechanisms and magnitude by which hypocaloric weight loss (WL) and aerobic exercise (AEX) affect body composition, glucose, lipid, muscle and adipose tissue metabolism in overweight, insulin resistant postmenopausal women. This will be tested in a trial comparing the effects of WL vs. AEX+WL on glucose, lipid, fat and muscle metabolism in overweight African American and Caucasian postmenopausal women with the following specific aims: 1. To determine whether there are racial (African American vs. Caucasian) and/or genetic differences in the effects of WL vs. AEX+WL on the metabolic actions of insulin on glucose, muscle, and fat metabolism by measuring insulin sensitivity, free fatty acid (FFA) suppression and insulin signaling proteins and activities in muscle biopsies during hyperinsulinemic-euglycemic clamps before and after the interventions. 2. To determine the cellular mechanisms by which the addition of AEX to WL affects insulin sensitivity in African American compared to Caucasian women by ascertaining the effects of WL vs. AEX+WL on proteins affecting insulin action (such as GLUT4, IRS1 and PI-3 kinase) in skeletal muscle (including micro-array technology), and insulin suppression of lipolysis in isolated adipocytes. 3. To determine whether there are racial differences in the skeletal muscle and adipose tissue metabolic responses to weight loss and exercise, and the changes in body composition, lipids and insulin sensitivity. 4. To determine whether genetic variation in the lipoprotein lipase (LPL) PvuII gene and/or other obesity-diabetes gene polymorphisms affect fasting LPL activity in muscle and adipose tissue and the metabolic responses to a hypocaloric diet, to alter the magnitude of the reduction in total and visceral fat, and glucose/insulin and lipoprotein lipids during longterm dietary-induced WL in obese postmenopausal women. 5. To determine in exploratory analyses if there are gene-race-environment interactions which affect insulin sensitivity and the response to weight loss and aerobic exercise or weight loss alone in African-American and Caucasian women.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。肥胖症的患病率在美国继续上升，据估计，人口中有1/3超重。非裔美国妇女的肥胖症发生率为49％，而白人妇女的发生率为33％。此外，非洲裔美国妇女的耐胰岛素耐药性要大得多，并且比高加索人的患病率是2型糖尿病的两倍。这些种族差异的原因并不能完全由肥胖的差异来解释。假设是存在种族（非裔美国人与高加索人）和遗传差异，其机制和幅度差异差异和有氧运动（AEX）会影响人体组成，葡萄糖，脂质，脂质，肌肉，肌肉，肌肉和脂肪糖组织的超级抗体，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素后，胰岛素后，胰岛素后代妇女。这将在一项试验中进行测试，以比较WL与AEX+WL对超重的非洲裔美国人和白种人的绝经后妇女的葡萄糖，脂质，脂肪和肌肉代谢的影响，具有以下具体目的：1。确定种族歧视（非洲裔美国人与/或遗传效应）是否存在种族差异。通过测量胰岛素敏感性，游离脂肪酸（FFA）抑制和胰岛素信号蛋白以及在干预之前和之后高胰岛素血糖糖夹期间的肌肉活检中的活性，葡萄糖，肌肉和脂肪代谢。 2。通过确定WL与AEX+WL对影响胰岛素作用的蛋白（例如Glut4，IRS1和PI-3激酶）在骨架肌肉中（包括Micro-rip in Intul in Intul in Intul in Intul-rip in Intul-rip in Intul-rip in Intul-rip），通过确定WL与AEX+WL对蛋白的影响，通过确定WL与AEX+WL对蛋白的影响，将AEX添加到WL中会影响非裔美国人的胰岛素敏感性，以及Instray Instrion Intrun Intul in Intul-rip in Intul-rip，脂肪细胞。 3。确定骨骼肌和脂肪组织代谢对体重减轻和运动的反应以及身体成分，脂质和胰岛素敏感性的变化是否存在种族差异。 4. To determine whether genetic variation in the lipoprotein lipase (LPL) PvuII gene and/or other obesity-diabetes gene polymorphisms affect fasting LPL activity in muscle and adipose tissue and the metabolic responses to a hypocaloric diet, to alter the magnitude of the reduction in total and visceral fat, and glucose/insulin and lipoprotein lipids during longterm肥胖的绝经后妇女饮食引起的WL。 5。在探索性分析中确定是否存在影响胰岛素敏感性以及对体重减轻和有氧运动或仅在非洲裔美国人和高加索妇女中单独进行有氧运动或体重减轻的反应的基因率环境相互作用。