Obesity, Inflammation, and Oxidative Stress

肥胖、炎症和氧化应激

• 批准号: 8102714
• 负责人: GLADYS BLOCK
• 金额: $ 65.65万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8102714
• 关键词: Adipose tissue; Aging; American Heart Association; Anti-Inflammatory Agents; Anti-inflammatory; Ascorbic Acid; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Centers for Disease Control and Prevention (U.S.); Chronic; Chronic Disease; Clinical Trials Design; Comorbidity; Cytokine Activation; Disease Resistance; Enrollment; Goals; Health; High Prevalence; Individual; Inflammation; Inflammatory; Insulin Resistance; Intervention Trial; Investigation; Measures; Metabolic syndrome; Non-Insulin-Dependent Diabetes Mellitus; Nutritional; Obesity; Oxidative Stress; Participant; Pathway interactions; Patients; Persons; Placebo Control; Placebos; Plasma; Population; Populations at Risk; Randomized; Randomized Controlled Trials; Research; Risk; Risk Factors; Sample Size; Sampling; Smoker; Source; Subgroup; Supplementation; Vitamin E; active method; arm; cardiovascular disorder risk; cost; cytokine; design; disorder prevention; high risk; inflammatory marker; non-smoker; public health relevance; randomized placebo controlled trial; treatment effect

DESCRIPTION (provided by applicant): The long-term objective of this project is to identify nutritional factors that can reduce the inflammatory component of obesity. Therapies to minimize obesity-related comorbidities are needed, and targeting inflammation may help slow the progression of obesity towards cardiovascular disease and insulin resistance. Adipose tissue is a source of inflammatory cytokines, and obesity is now viewed as a chronic, low-grade inflammatory state. Inflammation itself is a contributor to the chronic diseases associated with obesity. C- reactive protein (CRP) is a key marker of inflammation, and as a downstream marker it provides functional integration of upstream cytokine activation associated with inflammation. We have previously shown that vitamin C, but not vitamin E, reduces CRP in active and passive smokers and in nonsmokers. The reduction is seen primarily in persons with CRP e1.0 mg/L, the CDC threshold for elevated cardiovascular disease risk. We also found that 75% of obese nonsmokers had CRP e1.0 mg/L. The important observation of reduction in elevated CRP by vitamin C now needs to be confirmed in a rigorous study with adequate sample size, to permit justifiable conclusions about the potential usefulness of this agent in reducing inflammation in the obese. We will conduct a placebo-controlled, randomized trial in 552 healthy obese individuals with moderate CRP elevations (CRP e1.0 mg/L). Participants will be randomized to either 1000 mg/day vitamin C or placebo for a period of 2 months. We will also characterize the pathways through which this effect takes place by measuring cytokines and oxidative stress. This project is important because if our previous finding is confirmed in this population, it could offer a low-cost alternative to use of statins to reduce inflammation in persons without other risk factors. PUBLIC HEALTH RELEVANCE: Obesity is a prevalent inflammatory condition and major risk factor for many of the chronic diseases of aging. Confirming an anti-inflammatory effect of vitamin C is important because therapies to minimize obesity-related comorbidities are needed. Targeting the inflammatory component of obesity may help slow its progression towards insulin resistance and cardiovascular disease.

描述（由申请人提供）：该项目的长期目标是确定可以减少肥胖炎症成分的营养因子。需要最大限度地减少肥胖相关合并症的治疗，靶向炎症可能有助于减缓肥胖向心血管疾病和胰岛素抵抗的进展。脂肪组织是炎性细胞因子的来源，肥胖现在被视为慢性、低度炎症状态。炎症本身是与肥胖相关的慢性疾病的一个促成因素。C-反应蛋白（CRP）是炎症的关键标志物，并且作为下游标志物，其提供与炎症相关的上游细胞因子活化的功能整合。我们以前已经证明，维生素C，而不是维生素E，降低CRP在主动和被动吸烟者和非吸烟者。这种降低主要见于CRP e1.0 mg/L（CDC心血管疾病风险升高的阈值）的人群。我们还发现75%的肥胖非吸烟者CRP e 1.0 mg/L。通过维生素C降低CRP升高的重要观察结果现在需要在具有足够样本量的严格研究中得到证实，以允许关于该药剂在减轻肥胖者炎症中的潜在有用性的合理结论。我们将在552名CRP中度升高（CRP e1.0 mg/L）的健康肥胖个体中进行一项安慰剂对照、随机试验。参与者将随机接受1000 mg/天维生素C或安慰剂治疗2个月。我们还将通过测量细胞因子和氧化应激来表征这种效应发生的途径。这个项目很重要，因为如果我们之前的发现在这个人群中得到证实，它可以提供一种低成本的替代品来使用他汀类药物来减少没有其他危险因素的人的炎症。公共卫生相关性：肥胖是一种普遍的炎症性疾病，也是许多慢性衰老疾病的主要危险因素。证实维生素C的抗炎作用很重要，因为需要最大限度地减少肥胖相关合并症的治疗。针对肥胖的炎症成分可能有助于减缓其向胰岛素抵抗和心血管疾病的进展。