Understanding the relationship between obesity and tongue fat in humans and rats

睡眠呼吸暂停是一种常见疾病，发病率很高，至少影响4%的中年男性 2%的中年女性。肥胖被认为是阻塞性睡眠最重要的危险因素 然而，我们不知道肥胖是如何导致睡眠呼吸暂停的。并不是所有的肥胖受试者都有睡眠 呼吸暂停这项建议的重点是了解肥胖与肥胖之间的关系， 阻塞性睡眠呼吸暂停检查上气道结构（容积磁共振成像 研究）和功能（Pcrit和动态MRI）。具体来说，我们将：1）比较80个重量匹配的法线 在病例对照研究中，对80例呼吸暂停患者进行了研究; 2）直接检查减肥对60例呼吸暂停患者的影响， 手术减肥;和3）检查体重增加对肥胖和瘦Zucker和Sprague的影响- 道利老鼠。这项建议是基于总体假设，即睡眠呼吸暂停患者将有更多的 与体重匹配的对照组相比，舌头中的脂肪;体重减轻将减少舌头脂肪，增加 上呼吸道口径，使气道不那么塌陷; Zucker大鼠的体重增加将增加 我们的具体目标是：1）比较呼吸暂停患者的舌大小和肥胖 在性别分层、病例对照设计中， 确定这些舌头特性对气道口径、气道可膨胀性和 上呼吸道扩张肌的神经运动激活; 2）检查舌随时间的变化 大小和肥胖的呼吸暂停接受手术减肥，并确定的影响， 舌质变化对气道口径、AMI和气道通透性的影响; 3） 体重增加对腹部内脏脂肪（通过MRI测量）、舌脂肪（通过MRI测量） 和生物化学），舌头体积和气道大小在两个肥胖大鼠模型;遗传（Zucker） 和遗传-环境相互作用（Sprague-Dawley大鼠饮食诱导）。我们的资源， 包括先进MR成像技术（包括狄克逊成像和MR波谱）、新的容积成像技术、 计算机图像分析范例，强大的减肥手术计划和睡眠呼吸暂停的专业知识 生物统计学、啮齿动物成像研究、多导睡眠图和Pcrit将使我们能够实现我们的特定目标。

Sleep apnea is a common condition with significant morbidity that affects at least 4% of middle-aged males and 2% of middle-aged females. Obesity is thought to be the most important risk factor for obstructive sleep apnea yet we do not understand how obesity predisposes to sleep apnea. Not all obese subjects have sleep apnea. The focus of this proposal is directed towards understanding the relationship between obesity and obstructive sleep apnea by examining upper airway structure (volumetric magnetic resonance imaging studies) and function (Pcrit and dynamic MRI). Specifically we will: 1) compare 80 weight matched normals to 80 apneics in a case-control study; 2) directly examine the effect of weight loss on 60 apneics undergoing surgical weight loss; and 3) examine the effect of weight gain in obese and lean Zucker and Sprague- Dawley rats. This proposal is based on the overall hypotheses that patients with sleep apnea will have more fat in the tongue as compared to weight matched controls; weight loss will decrease tongue fat,increase upper airway caliber and make the airway less collapsible; and weight gain in Zucker rats will increase tongue size and tongue fat.Our specific aims are: 1) to compare tongue size and adiposity in apneics and obesity-matched controls without apnea in a gender-stratified, case-control design and determine the effects of these tongue properties on airway caliber, airway collapsibility and neuromotor activation of upper airway dilator muscles; 2) to examine changes over time in tongue size and adiposity in apneics undergoing surgical weight loss and to determine the effects of changes on tongue properties on airway caliber, AMIand airway collapsibility; and 3) to determine the effect of weight gain on abdominal visceral fat (measured by MRI), tongue fat (measured byMRI and biochemically), tongue volume, and airway size in two rat models of obesity; genetic (Zucker) and genetic-environmental interaction (diet-induced in Sprague-Dawley rats). Our resources, which include advanced MR imaging techniques (including Dixon imaging and MR spectroscopy), novel volumetric computer image analysis paradigms, a robust bariatric surgery program and expertise in sleep apnea biostatistics, rodent imaging studies, polysomnography, and Pcrit will allow us to achieve our specific aims.