A NONHUMAN PRIMATE MODEL FOR THE LINK BETWEEN CHILDHOOD ASTHMA & OBESITY

研究儿童哮喘之间联系的非人类灵长类动物模型

• 批准号: 8357830
• 负责人: ELIOT R SPINDEL
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357830
• 关键词: Allergic; American; Animals; Asthma; Body fat; Child; Childhood Asthma; Diet; Fatty Liver; Fatty acid glycerol esters; Funding; Grant; Human; Immune; Incidence; Inflammatory; Intervention; Link; Lung; Modeling; Monkeys; National Center for Research Resources; Obesity; Ovalbumin; Overweight; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Risk; Source; Structure; Therapeutic Intervention; United States National Institutes of Health; airway hyperresponsiveness; cost; cytokine; early onset; feeding; nonhuman primate; obesity in children; offspring; prevent; response; young adult

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The incidence of both childhood asthma and obesity has increased alarmingly in recent years. 17% of children are now obese and 35% are overweight. Multiple studies have clearly demonstrated that obesity increases the risk of developing childhood asthma but the underlying mechanisms are unknown and the optimum strategies to prevent the increased risk of asthma from obesity are also unknown. The purpose of this exploratory grant is to utilize a non-human primate model to characterize the link between early onset obesity and asthma as a first step in developing potential therapeutic interventions. This model uses young adult monkeys chronically fed a typical American high fat (HF) diet. The high fat diet offspring show increased body fat, fatty liver and increased cytokine levels, all of which are consistent with human childhood obesity. The basic hypothesis of this application is that the HF diet offspring will show increased bronchial reactivity to challenge with ovalbumin as well as evidence of increased Th2 activation and inflammatory cytokine expression. Four basic criteria are being examined to characterize the model: innate airway hyperreactivity; allergic hyperreactivity; systemic and lung immune and cytokine responses; and changes in airway structure and geometry. In the first year of this proposal, offspring of HF and normal diet animals are being studied. A key aspect of this study is to determine the ability of diet reversal interventions to reverse the airway reactivity changes induced by the HF diet and help break the link between obesity and asthma.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 近年来，儿童哮喘和肥胖的发病率都有惊人的增长。17%的儿童现在肥胖，35%超重。 多项研究已经清楚地表明，肥胖会增加儿童哮喘的风险，但其潜在机制尚不清楚，预防肥胖导致哮喘风险增加的最佳策略也不清楚。 这项探索性资助的目的是利用非人类灵长类动物模型来表征早发性肥胖和哮喘之间的联系，作为开发潜在治疗干预措施的第一步。 该模型使用年轻的成年猴，长期喂食典型的美国高脂肪（HF）饮食。 高脂肪饮食后代显示出增加的体脂、脂肪肝和增加的细胞因子水平，所有这些都与人类儿童肥胖一致。 本申请的基本假设是HF饮食后代将显示对卵清蛋白攻击的支气管反应性增加以及Th 2活化和炎性细胞因子表达增加的证据。 四个基本标准正在审查，以表征模型：先天性气道高反应性;过敏性高反应性;全身和肺免疫和细胞因子反应;和气道结构和几何形状的变化。 在该提案的第一年，正在研究HF和正常饮食动物的后代。 这项研究的一个关键方面是确定饮食逆转干预逆转HF饮食诱导的气道反应性变化的能力，并帮助打破肥胖和哮喘之间的联系。