Role of the CNS in the Metabolic Syndrome

中枢神经系统在代谢综合征中的作用

• 批准号: 7156709
• 负责人: John Michael Stafford
• 金额: $ 5.4万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156709
• 关键词: biological signal transduction; blood chemistry; central nervous system; disease /disorder onset; eating; glucose tolerance; glucose tolerance test; hyperlipidemia; hypertension; hypothalamus; insulin sensitivity /resistance; laboratory rat; leptin; metabolic syndrome; neuroendocrine system; neuroregulation; nuclear magnetic resonance spectroscopy; obesity; pathologic process; postdoctoral investigator; western blottings

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.

描述（由申请人提供）：过去 10 年，美国儿童超重的患病率增加了 50% 以上。通过从脂肪组织到 CMS 的信号通讯，通过负内分泌反馈回路严格调节体重。肥胖对健康的主要影响是代谢综合征，定义为腹部肥胖、血脂异常、高血压 (HTN) 和糖耐量受损 (IGT)。下丘脑回路参与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，b) 与由此产生的肥胖无关的代谢综合征特征。 Zucker脂肪大鼠（ZF）是具有肥胖、高血压、血脂异常和IGT的代谢综合征模型。我们的目标是通过确定产后发育中这些特征何时发生来确定下丘脑中的胰岛素和瘦素信号如何调节代谢综合征的特征。接下来，使用功能获得方法，我们将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生中起重要作用。