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

睡眠呼吸暂停是一种常见的疾病，发病率很高，至少有4%的中年男性受到影响。 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，我们还不知道肥胖是如何导致睡眠呼吸暂停的。并非所有肥胖的受试者都有睡眠 呼吸暂停。这项提案的重点是了解肥胖和 通过检查上呼吸道结构引起的阻塞性睡眠呼吸暂停(体积磁共振成像 研究)和功能(Pcrit和动态MRI)。具体来说，我们将：1)比较80个体重匹配的法线 对80例窒息患者进行病例对照研究；2)直接观察体重减轻对60例窒息患者的影响 手术减肥；以及3)检查肥胖和瘦Zucker和Sprague的体重增加的影响。 道利鼠。这项建议是基于睡眠呼吸暂停患者的总体假设。 舌头中的脂肪与体重匹配的对照组相比；减肥会减少舌头的脂肪，增加 上呼吸道口径，并使呼吸道更不容易折叠；Zucker大鼠的体重增加将增加 舌头大小和舌头脂肪。我们的具体目标是：1)比较窒息患者的舌头大小和肥胖程度 在性别分层的病例对照设计中，没有呼吸暂停的肥胖匹配对照研究 确定这些舌质对气道口径、气道溃散性和 上呼吸道扩张肌的神经运动激活；2)检查舌象随时间的变化 对接受手术减肥的窒息患者的体型和肥胖度的影响 舌质对气道口径、AM I和气道溃散性的影响；3)确定 体重增加对腹部内脏脂肪(MRI测量)、舌脂(MRI测量)的影响 在两种肥胖大鼠模型中，舌体积和呼吸道大小；遗传(Zucker) 遗传-环境交互作用(饮食诱导的Spraogue-Dawley大鼠)。我们的资源，这是 包括先进磁共振成像技术(包括Dixon成像和磁共振光谱学)、新的体积测量 计算机图像分析范例，一个强大的减肥手术程序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.