Role of the CNS in the Metabolic Syndrome

描述(由申请人提供)：在过去的10年里，美国超重儿童的流行率增加了50%以上。通过从脂肪组织向CMS传递信号，通过负内分泌反馈回路严格控制体重。肥胖的主要健康后果是代谢综合征，定义为腹型肥胖、血脂异常、高血压(HTN)和糖耐量减低(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)食物摄入量增加和肥胖，以及b)代谢综合征的特征与由此产生的肥胖无关。Zucker肥胖大鼠(ZF)是一种伴有肥胖、HTN、血脂异常和糖耐量低减的代谢综合征模型。我们的目标是确定胰岛素和瘦素在下丘脑中的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，使用功能增益方法，我们将确定下丘脑功能的恢复是否可以预防a)肥胖症和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.