AR CAREER DEVELOPMENT COBRE: THE ROLE OF LEPTIN IN OBESITY AND SLEEP

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 瘦素是一种由脂肪产生的激素，在调节能量摄入和支出方面发挥着关键作用。人类的瘦素水平在妊娠中期达到峰值，而啮齿动物的瘦素水平在出生后相当的发育时期达到峰值。这种上升早于对生长和生殖调节至关重要的垂体细胞(生长激素和促性腺激素)的增殖时间。青春期后，瘦素以振荡方式分泌，正常体型瘦素分泌周期为32次/24小时，峰值在午夜至凌晨3点之间。这项研究的重点是确定负责脉动性瘦素分泌的细胞。由于瘦素的上升与垂体生长激素的扩张相一致，我们将检验生长激素主要负责振荡脉冲的假设。为了验证这一假设，瘦素将通过创新的Cre-loxP技术在生长激素中选择性地消融。该缺失对瘦素分泌、夜间脉搏、促生长激素和促性腺激素发育的影响将在目标1研究中进行研究。目的2研究将集中在促生长激素瘦素在调节垂体促性腺激素和青春期时机中的潜在作用。目的3项研究将集中在夜间瘦素激增的意义上，并将包括研究瘦素在驱动睡眠的细胞事件中可能扮演的角色。瘦素对生长、生殖、能量节约和睡眠模式的重要性已经得到了充分的证实。肥胖可能与瘦素水平低和脉搏不正常有关。这项研究将解决瘦素在导致最佳身体成分和睡眠的正常事件中的作用，这将有助于我们理解导致肥胖的过程。阿赫特博士开发了瘦素分析，拟议中的研究将为独立的拨款申请提供初步数据，而赛义德博士将为他可以与阿赫特博士合作的另一项研究开发电生理技能。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Leptin is a hormone produced by fat that plays a key role in regulating energy intake and expenditure. Leptin levels rise to a peak at mid gestation in the human and during the equivalent postnatal period of development in the rodent. This rise precedes the timing of the proliferation of pituitary cells vital for the regulation of growth and reproduction (somatotropes and gonadotropes). After puberty, leptin is secreted in an oscillatory manner, with 32 pulses/24 hour period and peak amplitude between midnight and 3 AM in normal lean individuals. This study focuses on the identification of the cells responsible for the pulsatile leptin secretion. Because the leptin rise coincides with the expansion in pituitary somatotropes, we will test the hypothesis that somatotropes are mostly responsible for the oscillatory pulses. To test this hypothesis, leptin will be ablated selectively in somatotropes by innovative Cre-LoxP technology. The impact of this deletion on leptin secretion, nocturnal pulses and somatotrope and gonadotrope development will be investigated in Aim 1 studies. Aim 2 studies will focus on the potential role of somatotrope leptin in the regulation of pituitary gonadotropes and the timing of puberty. Aim 3 studies will focus on the significance of the nocturnal surge of leptin and will include an investigation of the role leptin may play in cellular events that drive sleep. Leptin's importance to growth, reproduction, energy conservation and sleep patterns is well established. Obesity may be correlated with low leptin and the absence of normal pulses. This study will address leptin's role in normal events that lead to optimal body composition and sleep, which will aid our understanding of processes that lead to obesity. Dr. Akhter has developed the leptin analyses and the proposed studies will provide the preliminary data for an independent grant application, while Dr. Syed will develop electrophysiological skills for a separate line of research in which he could collaborate with Dr. Akhter.