PHOTOPERIODIC CONTROL OF OBESITY

光周期控制肥胖

• 批准号: 2749444
• 负责人: Timothy Jon Bartness
• 金额: $ 12.5万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2749444
• 关键词: adipose tissue; bioenergetics; bioperiodicity; body composition; body temperature; caloric dietary content; circadian rhythms; denervation; disease /disorder model; hamsters; hormone regulation /control mechanism; innervation; insulin; lipid metabolism; melatonin; neuroendocrine system; obesity; photobiology; sympathetic nervous system

DESCRIPTION: Obesity is a disease of literally and figuratively enormous proportions. We have chosen a model of naturally occurring obesity-- photoperiod-induced seasonal obesity in Siberian hamsters (Phodopus sungorus sungorus). Siberian hamsters are naturally obese when housed in long "summer- like" days (LDs) and lose body mass, nearly exclusively as body fat, when exposed to short, "winter-like" days. After prolonged SD exposure and/or with increasing daylengths, body and lipid mass increase to their previous obese LD levels. Thus, the obesity is reversible. Three Specific Aims (SA) are proposed, each represented by a set of experiments. 1: What is the functional role of the sympathetic nervous system (SNS) in the photoperiod-induced differential decrease in white adipose tissue (WAT) mass and what is its CNS neuroanatomical substrate? We have demonstrated previously that a relatively separate direct SNS innervation exists for WAT pads. Experiments are designed to test further the separate neurologies associated with the SNS innervation of WAT and the function of this innervation. Therefore, we will answer the questions: 1) Can the SD-induced decreases in body fat occur independently of the SNS innervation of WAT? and 2) Does the relatively separate SNS innervation of WAT converge in the CNS? SA 2: What is the extent of the sensory innervation of WAT and what is its function in the photoperiod-induced changes in body fat? We have extended the initial observation of sensory innervation of WAT in laboratory rats to Siberian hamsters. However, in both studies, only subcutaneous WAT was tested for sensory innervation. In addition, we do not know the neurotransmitter phenotypes of these neurons, nor their function. Therefore, we will answer the questions: 1) What is the extent of the sensory innervation of WAT and what are the neurotransmitter phenotypes of the sensory neurons innervating this tissue? 2) What is the functional role of the sensory innervation of WAT in the SD-induced decreases in body fat? and 3) Is the SNS drive on the tissue increased following sensory denervation? SA 3: What are the neural contributions to total body fat regulation? We have shown that total body fat appears to be regulated based on the results of lipectomy experiments in Siberian hamsters; however, we do not know the mechanism underlying this regulation. Therefore, we will answer the following questions: 1) Is the SNS drive on the fat pads that show compensatory increases in fat pad mass decreased following lipectomy? 2) What is the role of the SNS innervation of WAT in the regulation of total body fat following lipectomy? and 3) What is the role of the sensory innervation of WAT in the regulation of total body fat by lipectomized hamsters? The results of these experiments should provide new information about the importance of the neural innervation of WAT, the regulation of total body fat and in the photoperiodic control of seasonal body fat cycles. In addition, insight into the fundamental processes involved in the development, maintenance and reversal of obesity also should occur.

描述：肥胖是一种字面上和形象上巨大的疾病 比例。 我们选择了一种自然发生的肥胖模型 - 西伯利亚仓鼠的光周期引起的季节性肥胖（phodopus 孙子）。 西伯利亚仓鼠自然是肥胖的 在漫长的“夏季”时代（LDS）和失去体重，几乎完全 作为体内脂肪，当暴露于短暂的“冬季”时代。 长时间 SD暴露和/或随着日长度的增加，身体和脂质质量 增加他们以前的肥胖LD水平。 因此，肥胖是 可逆。 提出了三个具体目标（SA），每个目标由 一组实验。 1：同情的功能作用是什么 光周期诱导的差异减少的神经系统（SNS） 在白色脂肪组织（WAT）质量中，其CNS神经解剖学是什么 底物？ 我们以前已经证明了一个相对分开的 直接SNS神经存在用于WAT垫。 设计实验 进一步测试与SNS相关的单独神经系统 WAT的神经和此神经的功能。 因此，我们 会回答问题：1）SD诱导的人体脂肪可以减少 独立于WAT神经支配而发生？ 2） 中枢神经系统中的WAT汇聚相对分开的SN神经？ SA 2： WAT的感觉神经的程度是多少？ 在光周期引起的体内脂肪变化中的功能？ 我们有 扩展了对WAT的感觉神经的初始观察 实验室老鼠到西伯利亚仓鼠。 但是，在这两项研究中，只有 皮下WAT测试了感觉神经。 另外，我们 不知道这些神经元的神经递质表型，也不知道 功能。 因此，我们将回答问题：1） WAT的感觉神经的程度，什么是 感觉神经元的神经递质表型 组织？ 2）感觉神经的功能作用是什么 SD引起的体内脂肪的降低？ 3）是SNS驱动器 在感官神经支配之后，组织上有增加吗？ SA 3：什么是 对总体脂肪调节的神经贡献？ 我们已经显示了 总体脂肪似乎是根据 西伯利亚仓鼠的脂肪切除术实验；但是，我们不知道 该法规的基础机制。 因此，我们将回答 以下问题：1）在显示的脂肪垫上的SNS驱动器是 脂肪切除术后脂肪垫质量的补偿性增加？ 2）WAT的SN神经在调节中的作用是什么 脂肪切除术后全身脂肪？ 3） WAT在总体脂肪调节中的感觉神经 脂肪切除的仓鼠？ 这些实验的结果应提供 有关WAT神经神经神经的重要性的新信息， 调节全身脂肪和光周期控制 季节性身体脂肪周期。 此外，洞悉基本 与开发，维护和逆转有关的过程 肥胖也应该发生。