ROLE OF LEPTIN IN THE REGULATION OF LEUKOTRIENE LEVELS IN ASTHMA

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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.'