PHOTOPERIODIC CONTROL OF OBESITY

光周期控制肥胖

• 批准号: 2139530
• 负责人: Timothy Jon Bartness
• 金额: $ 12.67万
• 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 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2139530
• 关键词: PHOTOPERIODIC; CONTROL; OBESITY

Obesity is a disease of figuratively and literally enormous proportions. Women with male-type body fat distribution exhibit an exaggeration of the secondary health consequences of obesity such as increased probability of cardiovascular disease, stroke, non-insulin dependent diabetes mellitus and carcinomas. The study of traditional animal models of human obesity have left considerable gaps in our knowledge of the mechanisms underlying body fat distribution and deposition. It has been suggested that species that show naturally-occurring changes in body and lipid mass cycles may be valuable in the study of obesity. The Siberian hamster (Phodopus sungorus sungorus) is one such species. In long, summer-like photoperiods they are naturally obese; however, when they are transferred to short, winter-like photoperiods they lose body mass, nearly exclusively as body fat. After prolonged short day exposure and/or with increasing daylengths, body and lipid mass increase to their previous obese state. Thus, this is a reversible, naturally-occurring obesity that is convenient to study because it is completely under the control of the daylength. The overall purpose of the proposed research is to examine the photoperiod-induced control of regional fat pad-specific changes in lipid storage and how this process contributes to the seasonally appropriate 'regulation' of total body fat. In addition, the impact of this regulation on energy balance (i.e., food intake and thermogenesis) will be examined. Three specific aims are proposed, each represented by a set of experiments. Specific Aim 1: Are the photoperiodic changes in total body fat 'regulated' and what mechanisms underlie this process? Levels of body fat will be manipulated to see if seasonally appropriate adjustments are made to these challenges. Body fat compensation, neural and hormonal influences and changes in energy input and output will be assessed. Specific Aim 2: What hormones or autocrine/paracrine factors mediate the photoperiodic control of body and lipid mass, lipid metabolism and energy balance? Several hormones or autocrine/paracrine factors affected by the photoperiod will be examined for their influence on body and lipid mass (fat distribution), lipid metabolism and energy balance. Specific Aim 3: What is the role of the sympathetic nervous system (SNS) in the photoperiodic control of body and lipid mass, lipid metabolism, an energy balance? The type and extent of the innervation of white adipose tissue (WAT) will be examined using neuronal tract-tracing techniques. Confirmation of innervation and tests of its function will be done using selective surgical denervation. Photoperiod-induced, region-specific changes in the control of lipolysis (fat breakdown) in WAT pads by the SNS will be examined and will include measurement of changes in adipocyte adrenergic receptors, norepinephrine turnover, and in vivo and in vitro lipolytic rates. This multidisciplinary approach should provide new information about the photoperiodic influences on body and lipid mass, lipid metabolism and energy balance that may reflect fundamental processes in the development, maintenance and reversal of obesity.

肥胖是形象上和字面上的巨大比例疾病。 男性型体内脂肪分布的女性表现出夸张的夸张 肥胖的二级健康后果，例如增加的可能性 心血管疾病，中风，非胰岛素依赖性糖尿病和 癌。 对人类肥胖传统动物模型的研究有 在我们对机构基础机制的了解中留下了很大的差距 脂肪分布和沉积。 有人建议种种 显示身体和脂质质量周期的自然变化可能是 在肥胖研究中很有价值。 西伯利亚仓鼠（Phodopus Sungorus Sungorus）就是一种这样的物种。 在漫长的夏季般的光周期中它们是 自然肥胖；但是，当它们被转移到短暂的冬季时 光周期它们失去体重，几乎完全是体内脂肪。 后 长时间的短一天暴露和/或日间长度增加，身体和/或 脂质质量增加到以前的肥胖状态。 因此，这是一个 可逆的，自然的肥胖症，很方便地学习，因为 它完全由日程控制。 总体目的 拟议的研究是检查光周期诱导的对 脂质存储的区域脂肪垫特异性变化以及该过程如何 有助于总体脂肪的季节性“调节”。 另外，该法规对能量平衡的影响（即食物 将检查摄入量和热生成）。 三个具体目标是 提出的，每个都由一组实验表示。 具体目标1：是 总体脂肪“调节”的光周期变化以及哪些机制 这是这个过程的基础？ 会操纵体内脂肪的水平，以查看是否 对这些挑战进行了适当的调整。 体内脂肪 补偿，神经和荷尔蒙影响和能量输入的变化 并将评估产出。 特定目标2：什么激素或 自分泌/旁分泌因子介导人体的光周期控制和 脂质质量，脂质代谢和能量平衡？ 几种激素或 将检查受光周期影响的自分泌/旁分泌因子 因为它们对身体和脂质质量（脂肪分布）的影响，脂质 代谢和能量平衡。 特定目标3： 人体光周期控制中的交感神经系统（SNS） 脂质质量，脂质代谢，能量平衡？ 的类型和程度 将使用白色脂肪组织（WAT）的神经 神经元路追踪技术。 神经和测试的确认 它的功能将使用选择性手术神经治疗来完成。 光周期诱导的，区域特异性的脂解控制 （脂肪分解）将检查SNS的WAT垫，并将包括 测量脂肪细胞肾上腺素能受体的变化，去甲肾上腺素 营业额以及体内和体外脂肪率。 这个多学科 方法应提供有关光周期影响的新信息 在身体和脂质质量上，脂质代谢和能量平衡可能 反映开发，维护和逆转的基本过程 肥胖。