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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 瘦素是一种由脂肪产生的激素，在调节能量摄入和消耗方面起着关键作用。瘦素水平在人类妊娠中期和啮齿动物出生后发育期达到峰值。这种上升先于垂体细胞增殖的时间，垂体细胞对生长和生殖的调节至关重要（生长激素和促性腺激素）。青春期后，瘦素以振荡的方式分泌，在正常瘦个体中，每24小时周期有32个脉冲，峰值幅度在午夜至凌晨3点之间。本研究的重点是确定负责脉冲式瘦素分泌的细胞。由于瘦素的增加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，瘦素将选择性消融在生长激素的创新Cre-LoxP技术。 将在目标1研究中研究这种缺失对瘦素分泌、夜间脉搏以及生长激素和促性腺激素发育的影响。 目的2研究瘦素对垂体促性腺激素的调节及青春期发育的影响。 目标3的研究将集中在夜间激增的瘦素的意义，并将包括调查瘦素可能在驱动睡眠的细胞事件中发挥的作用。 瘦素对生长、繁殖、能量保存和睡眠模式的重要性已经得到了充分的证实。 肥胖可能与低瘦素和缺乏正常脉搏有关。这项研究将解决瘦素在正常事件中的作用，导致最佳的身体组成和睡眠，这将有助于我们理解导致肥胖的过程。 Akhter博士已经开发了瘦素分析，拟议的研究将为独立的资助申请提供初步数据，而Syed博士将为他可以与Akhter博士合作的单独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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.