Role of the CNS in the Metabolic Syndrome

描述（由申请人提供）：在过去10年中，美国超重儿童的患病率增加了50%以上。体重通过从脂肪组织到CMS的信号通信通过负内分泌反馈回路被严格调节。肥胖的主要健康后果是代谢综合征，其定义为腹部肥胖、血脂异常、高血压（HTN）和葡萄糖耐量受损（IGT）。下丘脑回路参与了所有这些特征的调节。我们假设CMS对胰岛素和瘦素的抵抗导致：a）食物摄入增加和肥胖，和B）代谢综合征的特征独立于所导致的肥胖。Zucker肥胖大鼠（ZF）是具有肥胖、HTN、血脂异常和IGT的代谢综合征的模型。我们的目标是确定下丘脑中胰岛素和瘦素信号如何调节代谢综合征的特征，通过确定这些特征在产后发育中何时发生。接下来，我们将使用功能获得方法来确定下丘脑功能的恢复是否可以预防a）肥胖和B）代谢综合征的发生。因此，中枢神经系统对胰岛素和瘦素的抵抗可能在儿童和青少年肥胖和代谢综合征的发展中起重要作用。

DESCRIPTION (provided by applicant): The prevalence of overweight children in the US has increased by more than 50% in the last 10 years. Body weight is tightly regulated through a negative endocrine feedback loop by communication of signals from adipose tissue to the CMS. The major health consequence of obesity is metabolic syndrome, defined as abdominal obesity, dyslipidemia, hypertension (HTN), and impaired glucose tolerance (IGT). Hypothalamic circuits are involved in the regulation of all of these traits. We hypothesize that CMS resistance to insulin and leptin leads; a) to increased food intake and obesity, and b) to traits of metabolic syndrome independent of the resultant obesity. The Zucker fatty rat (ZF) is a model of metabolic syndrome with obesity, HTN, dyslipidemia, and IGT. Our objective is to determine how insulin and leptin signaling in the hypothalamus regulates the traits of metabolic syndrome by determining when in post-partum development these traits occur. Next, using a gain-of-function approach we will determine if restoration of hypothalamic function can prevent the onset of a) adiposity and b) metabolic syndrome. Thus CNS resistance to insulin and leptin may be important in the development of obesity and metabolic syndrome in children and adolescents.