OBESITY AND AIRWAY RESPONSIVENESS

有证据表明，肥胖会增加患上 哮喘，但这种联系的机制基础是未知的。虽然变化 呼吸系统的机制可以解释这种现象， 初步数据提出了一个新的假设，即肥胖通过以下途径促进AHR： 瘦素诱导的炎症增加。荷尔蒙瘦素被释放出来 并对进食和能量消耗具有下丘脑作用。 血清瘦素与肥胖相关，在肥胖人群中升高。 初步数据表明，由于遗传缺陷而导致的小鼠肥胖 在羧肽酶E（Cpefat小鼠）和具有高血清瘦素、臭氧 (O3)引起的气道炎症增加。然而，肥胖似乎 本身并不促进AHR，因为O3诱导的气道高反应性（AHR） 在缺乏瘦素基因的小鼠中， 瘦素受体，即使这些小鼠明显肥胖。为了验证这一 假设，O3和变应原诱导的AHR和气道炎症的测量 将在因瘦素缺乏而肥胖的小鼠中进行 基因（ob/ob）或瘦素受体（db/db），以及肥胖但具有 高瘦素水平（肥胖、肥胖和肥胖小鼠以及高脂肪饮食小鼠）。在 此外，将外源性瘦素给予对照和ob/ob小鼠， 急性增加血清瘦素，或对照小鼠禁食过夜，以急性 降低血清瘦素水平，并检测对AHR和气道炎症的影响。如果 瘦素的促炎作用有助于肥胖诱导的AHR，然后是O3 在高剂量的小鼠中，过敏原诱导的AHR和炎症应增强。 瘦素水平和接受外源性瘦素的小鼠，但在ob/ob中降低 和db/db小鼠以及禁食小鼠。理解机械基础， 肥胖受试者哮喘风险增加可能导致新的公共卫生 治疗哮喘的策略或治疗方式。

There is evidence that obesity increases the risk of developing asthma, but the mechanistic basis for this link is unknown. Although changes in the mechanics of the respiratory system could explain this phenomenon, preliminary data suggest a novel hypothesis, that obesity promotes AHR through leptin induced augmentation of inflammation. The hormone leptin is released from adipocytes and has hypothalamic effects on eating and energy expenditure. Serum leptin correlates with adiposity and is increased in obese humans. Preliminary date indicate that in mice obese as a result of a genetic deficit in carboxypeptidase E (Cpefat mice) and which have high serum leptin, ozone (O3) induced airway inflammation is increased. However it appears that obesity per se does not promote AHR since O3-induced airway hyperresponsiveness (AHR) is reduced in mice that are genetically deficient in either leptin itself or the leptin receptor, even though the mice are markedly obese. To test this hypothesis, measurements of O3 and allergen-induced AHR and airway inflammation will be made in mice that are obese as a result of deficiencies in the leptin gene (ob/ob) or the leptin receptor (db/db), and mice that are obese but have high leptin levels (fat, tub and agouti mice and mice on high fat diets). In addition, exogenous leptin will be administered to control and ob/ob mice to acutely increase serum leptin, or control mice fasted overnight to acutely decrease serum leptin, and effects on AHR and airway inflammation examined. If pro-inflammatory effects of leptin contribute to obesity induced AHR, then O3 and allergen-induced AHR and inflammation should be enhanced in mice with high leptin levels and in mice that receive exogenous leptin, but reduced in ob/ob and db/db mice and in fasted mice. Understanding the mechanistic basis for the increased risk of asthma in obese subjects might lead to new public health strategies or therapeutic modalities for the treatment of asthma.