Gender Obesity C-Reactive Protein and Oxidative Stress

性别肥胖 C 反应蛋白和氧化应激

• 批准号: 6882648
• 负责人: GLADYS BLOCK
• 金额: $ 63.57万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-15 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882648
• 关键词: acute phase protein; adipose tissue; age difference; antioxidants; ascorbate; biomarker; blood chemistry; body composition; clinical research; clinical trials; colorimetry; dietary supplements; gas chromatography; gender difference; high performance liquid chromatography; human subject; nutrition related tag; obesity; oxidative stress; peroxidation; photon absorptiometry; postmenopause; questionnaires; statistics /biometry; tocopherols

DESCRIPTION (provided by applicant): The long-term objective of this project is to identify nutritional factors that can lower C-reactive protein and lipid peroxidation. C-reactive protein (CRP), a marker of inflammation, has been shown to be "remarkably consistent" in its association with cardiovascular disease, as well as with diabetes and other conditions. Oxidative damage biomarkers have been associated with the etiology of numerous disease conditions, including atherosclerosis, diabetes, COPD and others. Both CRP and lipid oxidation have been shown to have a direct (not correlational) effect on vascular and other tissues, including effects on smooth muscle contractility, induction of intercellular and vascular cell adhesion molecules, enhancement of complement activation, and other mechanisms. We hypothesize that some of the harmful effects of obesity, and of post-menopausal status, are attributable to fat induced CRP and lipid oxidation. We propose to test whether antioxidant supplements can lower CRP and lipid oxidation. In a previous randomized trial we found that antioxidant supplementation significantly lowered CRP and lipid peroxidation. That study also found higher baseline CRP and lipid peroxidation in women compared to men, and in obese persons compared to those of normal weight. The previous intervention study did not measure body fat (except as BMI), assess menopause status, or intervene on persons who neither smoked nor were passively exposed. We now propose a study in nonsmokers, to test whether antioxidant supplements can lower CRP and oxidative damage. In the baseline data prior to intervention, we will determine whether the higher oxidation and CRP in women and overweight persons can be confirmed in persons with no smoke exposure, after adjustment for covariates. We will conduct a randomized placebo-controlled trial to test the following specific aims: 1. To determine whether antioxidant supplementation can lower C-reactive protein (CRP) and lipid peroxidation. 1a. To determine whether one antioxidant is significantly more effective than the other. 1b. To determine whether treatment effects differ by gender or body fat 2. To determine whether there are gender or body fat differences in baseline CRP or in baseline lipid peroxidation, in nonsmokers, independent of other covariates. 2a. In women, to determine whether postmenopausal status is associated with higher baseline CRP or lipid peroxidation, after control of covariates.

描述(申请人提供)：该项目的长期目标是确定可以降低C-反应蛋白和脂质过氧化的营养因素。C-反应蛋白(CRP)，一种炎症的标志，已经被证明与心血管疾病以及糖尿病和其他疾病的联系“非常一致”。氧化损伤生物标记物与许多疾病的病因有关，包括动脉粥样硬化、糖尿病、慢性阻塞性肺病和其他疾病。C反应蛋白和脂质氧化都被证明对血管和其他组织有直接的(不相关的)影响，包括对平滑肌收缩、诱导细胞间和血管细胞黏附分子、增强补体激活等机制的影响。我们假设肥胖和绝经后状态的一些有害影响可归因于脂肪诱导的C反应蛋白和脂质氧化。我们建议测试抗氧化剂补充剂是否可以降低CRP和脂质氧化。 在先前的随机试验中，我们发现补充抗氧化剂显着降低了CRP和脂质过氧化。该研究还发现，与男性相比，女性的基线CRP和脂质过氧化水平更高，与正常体重的人相比，肥胖者的基线CRP和脂质过氧化水平更高。 之前的干预研究没有测量体脂(BMI除外)，没有评估更年期状态，也没有对既不吸烟也不被动暴露的人进行干预。我们现在提议在非吸烟者中进行一项研究，以测试抗氧化剂补充剂是否可以降低CRP和氧化损伤。在干预前的基线数据中，我们将确定在调整协变量后，是否可以在没有吸烟暴露的人中证实女性和超重者的氧化和C反应蛋白水平较高。 我们将进行一项随机的安慰剂对照试验，以测试以下具体目标： 1.确定补充抗氧化剂是否能降低C-反应蛋白(CRP)和脂质过氧化作用。 1A.以确定其中一种抗氧化剂是否明显比另一种更有效。 1B.确定治疗效果是否因性别或体脂不同而不同 2.在非吸烟者中，独立于其他协变量，确定基线CRP或基线脂质过氧化水平是否存在性别或体脂差异。 2A。在女性中，在控制协变量后，确定绝经后状态是否与较高的基线CRP或脂质过氧化有关。