Role of Vagal Afferents in Maintainence of Body Weight and Glucose Homeostasis

描述（由申请人提供）：代谢失调疾病是发展中国家的主要公共卫生问题。肥胖与多种健康问题相关，并且被认为是一种日益增长的流行病，而II型糖尿病的发病率持续上升。肠-脑轴的许多紊乱，或中枢神经通路对消化系统信息的反应，与肥胖和II型糖尿病有关。然而，对于来自外周的信息到达这些中心稳态位点的途径，我们知之甚少。一些证据表明，迷走神经传入神经可能在能量稳态的神经调节中发挥关键作用。揭示这些途径可能会导致治疗能量平衡功能障碍的新靶点。本文提出的研究试图在小鼠中使用遗传和药理学操作的组合，其允许特异性消融迷走神经感觉神经元，确定迷走神经传入是否是在食物喂养和饮食诱导的肥胖中维持长期体重和葡萄糖稳态所需的，如果迷走神经传入是噻唑烷二酮类的抗糖尿病作用所需的，以及迷走神经传入对于CB 1 R拮抗剂类药物的抗糖尿病作用是否是必需的。

DESCRIPTION (provided by applicant): Diseases of metabolic dysregulation are major public health concerns in the developing world. Obesity is associated with multiple health problems and is being recognized as a growing epidemic, while incidence of Type II diabetes continues to rise. Many derangements in the gut-to-brain axis, or the response of central neural pathways to information from the digestive system, have been implicated in obesity and Type II diabetes. However, relatively little is known about the pathways by which information from the periphery reaches these central homeostatic sites. Several lines of evidence suggest that the afferent vagal nerve may play a key role in neural regulation of energy homeostasis. Uncovering these pathways may result in new targets for treatment of energy balance dysfunction. The studies proposed here seek to, using a combination of genetic and pharmacologic manipulations in mice which allow for specific ablation of vagal sensory neurons, determine whether vagal afferents are required for the maintenance of long-term body weight and glucose homeostasis under chow feeding and in diet-induced obesity, if vagal afferents are required for the anti-diabetic actions of thiazolidinediones, and if vagal afferents are necessary for the anti-diabetic action of the CB1R antagonist class of drugs.