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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 近年来，儿童哮喘和肥胖症的发病率都有惊人的增长。17%的儿童现在肥胖，35%的儿童超重。多项研究清楚地表明，肥胖会增加儿童哮喘的风险，但潜在的机制尚不清楚，预防肥胖导致哮喘风险增加的最佳策略也是未知的。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和哮喘之间的联系，作为开发潜在治疗干预措施的第一步。这个模型使用的是长期以典型的美国高脂肪(HF)饮食喂养的成年幼猴。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，所有这些都与人类童年肥胖的情况一致。这一应用的基本假设是，HF饮食后代将表现出对卵清蛋白挑战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描述该模型：固有的呼吸道高反应性；过敏性高反应性；全身和肺免疫和细胞因子反应；以及呼吸道结构和几何形状的变化。在这项提议的第一年，将对HF和正常饮食动物的后代进行研究。这项研究的一个关键方面将是确定饮食逆转干预的能力，逆转由HF饮食引起的呼吸道反应性变化，并帮助打破肥胖和哮喘之间的联系。

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.