ROLE OF LEPTIN IN THE REGULATION OF LEUKOTRIENE LEVELS IN ASTHMA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 最近的研究表明，阻塞性肺病（如哮喘或慢性支气管炎）与肥胖之间存在正相关。肥胖还与气道对刺激物的反应性增加相关。相比之下，体重减轻与肺功能的改善和对刺激物反应的气道狭窄减少有关。脂肪衍生因子，瘦素，与身体脂肪储存相关，在肥胖症中增加。肥胖的慢性支气管炎患者瘦素水平升高，体重减轻的肺气肿患者瘦素水平降低。炎症因子，白三烯，在体重过轻的受试者中减少。已知这些白三烯参与哮喘的发展。我们的实验室最近注意到，脂肪衍生因子，瘦素，调节有助于制造白三烯的酶。我们已经证明，在缺乏瘦素的动物的肺中的白色细胞中白三烯水平降低。此外，向这些白色细胞中添加瘦素可以恢复白三烯水平。这项建议的目的是研究肥胖在哮喘病因中的作用。该方法将检查正常体重和患有哮喘但其他健康的肥胖人群。我们将确定瘦素在调节血液白色细胞和肺中白三烯水平中的作用。这一建议的意义在于对哮喘病因的新认识和新的治疗方法的发展。'

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. Recent studies showed a positive association between obstructive lung disease, such as asthma or chronic bronchitis, and obesity. Obesity is also independently associated with increased airway narrowing in response to irritants. By contrast, weight loss is associated with improved lung function and reduced airway narrowing in response to irritants. The fat-derived factor, leptin, which correlates with body fat stores, is increased in obesity. Increased leptin occurs in chronic bronchitis patients with obesity, and is decreased in emphysema patients with reduced weight. The inflammatory factors, leukotrienes, are reduced in subjects that are underweight. These leukotrienes are known to be involved in the development of asthma. Our laboratory has recently noted that the fat-derived factor, leptin, regulates the enzyme that helps make leukotriene. We have demonstrated that leukotriene levels are decreased in white cells in the lung from animals deficient in leptin. Furthermore, adding back leptin to these white cells restores leukotriene levels. The objective of this proposal is to examine the role obesity plays in the causation of asthma. The approach will be to examine normal weight and obese humans who have asthma but otherwise healthy. We will determine the role leptin plays in regulating leukotriene levels in blood white cells and the lung. The significance of this proposal lies in the potential for new insights into causation of asthma and in the development of novel methods of treatment.'