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比喻上都影响巨大的疾病。 比例。 我们选择了一个自然发生的肥胖模型—— 光周期诱导的西伯利亚仓鼠季节性肥胖（Phodopus 桑戈鲁斯 桑戈鲁斯）。 西伯利亚仓鼠在饲养时自然肥胖 在漫长的“夏季”日子（LD）中，几乎完全失去了体重 当暴露于短暂的“冬天般”的日子时，身体脂肪就会增加。 经过长时间的 SD 暴露和/或随着日照长度、身体和脂质质量的增加 增加到之前肥胖的 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：交感神经的功能是什么 神经系统（SNS）中光周期引起的差异减少 白色脂肪组织 (WAT) 肿块及其中枢神经系统神经解剖学是什么 基材？ 我们之前已经证明了一个相对独立的 WAT 垫存在直接 SNS 神经支配。 实验设计 进一步测试与 SNS 相关的单独神经学 WAT 的神经支配以及该神经支配的功能。 因此，我们 将回答以下问题： 1) SD 能否引起体内脂肪减少 独立于 WAT 的 SNS 神经支配而发生？ 2) 是否 WAT 相对独立的 SNS 神经支配在 CNS 中汇聚？ SA 2： WAT的感觉神经支配范围是多少，其作用是什么？ 在光周期引起的体内脂肪变化中发挥作用？ 我们有 扩展了 WAT 感觉神经支配的初步观察 实验室老鼠和西伯利亚仓鼠。 然而，在这两项研究中，仅 测试皮下 WAT 的感觉神经支配。 此外，我们 不知道这些神经元的神经递质表型，也不知道它们的 功能。 因此，我们将回答以下问题：1）什么是 WAT 感觉神经支配的程度以及什么是 支配该感觉神经元的神经递质表型 组织？ 2) 感觉神经支配的功能是什么 SD 中的 WAT 会导致体内脂肪减少吗？ 3）是SNS驱动器 感觉去神经支配后组织的增加？ SA 3：什么是 神经对全身脂肪调节的贡献？ 我们已经展示了 全身脂肪似乎是根据以下结果进行调节的 西伯利亚仓鼠的脂肪切除实验；然而，我们不知道 这一监管的机制。 因此，我们将回答 以下问题： 1）SNS 驱动器是否显示在脂肪垫上 脂肪切除术后脂肪垫质量的代偿性增加减少？ 2）WAT的SNS神经支配在调节中的作用是什么？ 脂肪切除术后的全身脂肪含量？ 3) 的作用是什么 WAT 的感觉神经支配对全身脂肪的调节 仓鼠做了脂肪切除术吗？ 这些实验的结果应该提供 关于 WAT 神经支配重要性的新信息， 全身脂肪的调节和光周期控制 季节性体脂周期。 另外，深入了解基本面 涉及开发、维护和逆转的过程 肥胖也应该发生。