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: 8173328
• 负责人: ELIOT R SPINDEL
• 金额: $ 7.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173328
• 关键词: Allergic; American; Animals; Asthma; Body fat; Child; Childhood Asthma; Computer Retrieval of Information on Scientific Projects Database; Diet; Fatty Liver; Fatty acid glycerol esters; Funding; Grant; Human; Immune; Incidence; Inflammatory; Institution; Intervention; Link; Lung; Modeling; Monkeys; Obesity; Ovalbumin; Overweight; Research; Research Personnel; Resources; Risk; Source; Structure; Therapeutic Intervention; United States National Institutes of Health; airway hyperresponsiveness; 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. 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 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 application 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 will be 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 will be studied. A key aspect of this study will be 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 近年来，儿童哮喘和肥胖症的发病率急剧增加。 目前，17% 的儿童肥胖，35% 的儿童超重。 多项研究清楚地表明，肥胖会增加患儿童哮喘的风险，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未知。 这一探索性应用的目的是利用非人类灵长类动物模型来表征早发性肥胖与哮喘之间的联系，作为开发潜在治疗干预措施的第一步。 该模型使用长期喂食典型美国高脂肪 (HF) 饮食的年轻成年猴子。 高脂肪饮食的后代表现出体脂增加、脂肪肝和细胞因子水平增加，所有这些都与人类儿童期肥胖相符。 该应用的基本假设是，HF饮食的后代将表现出对卵清蛋白攻击的支气管反应性增加，以及Th2激活和炎性细胞因子表达增加的证据。 将检查四个基本标准来表征该模型：先天性气道高反应性；过敏性高反应;全身和肺部免疫和细胞因子反应；以及气道结构和几何形状的变化。 在该提案的第一年，将研究 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措施逆转高频饮食引起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。