Environmental temperature, SNS development and obesity

描述(从申请者的描述中扫描)：长期目标 这个项目是为了确定在开发过程中环境暴露如何 有助于成人获得肥胖或高血压的特征。如果 如果成功，就有可能制定出早期干预的策略。 这可能会预防或至少阻止这些疾病的发展。 本申请中提出的研究解决了 胎儿和新生儿生活中的几个环境因素(环境 体温、母亲饮食和产前对糖皮质激素的暴露) 动物成年后易患肥胖症。这是一场关于 申请者认为，这三种暴露会导致不同的肥胖倾向 通过改变交感肾上腺功能的特定方面，以及 食物摄入量可能增加。申请者建议及早接触 降低环境温度会使动物容易肥胖 没有所谓的代谢综合征的特征，而母体 摄入合成饲料会使类似的动物更容易发育 肥胖伴随着“代谢综合征”。申请者还预测， 产前接触糖皮质激素将加剧任何其他倾向 其后代会患上与肥胖相关的“代谢综合征”。 此外，由于这些暴露并不是相互排斥的， 申请人提出，母亲接触糖皮质激素和 合成饮食将协同作用，以夸大 后代患上肥胖症和“代谢综合征”。此外，由于 中缝苍白带内交感前运动神经元对棕色脂肪的脑干定位 (RPA)也可能有助于调节葡萄糖代谢，它是 假设激活或抑制RPA将产生相应的 葡萄糖处置的变化。申请者建议使用技术 去甲肾上腺素(NE)周转率与尿儿茶酚胺水平的关系 非麻醉状态下交感神经和肾上腺髓质功能 并利用对脉冲交通的神经生理学研究 观察RPA在麻醉大鼠交感神经纤维中的作用 通过特定刺激，如胰岛素和瘦素，介导SNS的激活。这个 RPA调节交感神经活动变化的潜在影响 还将检查葡萄糖和能量代谢。

DESCRIPTION (Scanned from the Applicant's Description): The long-term goal of this project is to determine how environmental exposures during development contribute to the acquisition of obese or hypertensive traits in the adult. If successful, it may be possible to devise strategies for early intervention which might prevent or at least forestall the development of these disorders. The studies proposed in this application address the lasting influence of several environmental factors during fetal and neonatal life (environmental temperature, maternal diet and prenatal exposure to glucocorticoids) on an animal's susceptibility to become obese as an adult. It is the contention of the applicants that these three exposures induce different obesity-prone phenotypes by altering specific aspects of sympathoadrenal function, along with possible increases in food intake. The applicants propose that early exposure to cool environmental temperatures will predispose animals to develop obesity without features of the so-called 'metabolic syndrome', while maternal ingestion of a synthetic diet will predispose similar animals to develop obesity along with the 'metabolic syndrome'. The applicants also predict that prenatal exposure to glucocorticoids will exacerbate any other tendencies in the offspring to develop the 'metabolic syndrome' in conjunction with obesity. Furthermore, since these exposures are not mutually exclusive of one another, the applicants propose that maternal exposure both to glucocorticoids and to a synthetic diet will interact synergistically to exaggerate tendencies in the offspring toward obesity and the 'metabolic syndrome'. In addition, since the brainstem locus for sympathetic premotoneurons to brown fat in raphe pallidus (RPa) may also contribute to regulation of glucose metabolism, it is hypothesized that activation or inhibition of RPa will produce corresponding changes in glucose disposal. The applicants propose to use techniques of norepinephrine (NE) turnover and urine catecholamine levels to assess sympathetic and adrenal medullary function, respectively, in unanesthetized animals and to utilize neurophysiological studies of impulse traffic in sympathetic fibers of anesthetized rats to examine the importance of RPa in mediating SNS activation by specific stimuli, such as insulin and leptin. The potential impact of changes in sympathetic activity regulated by RPa for glucose and energy metabolism will also be examined.