PHOTOPERIODIC CONTROL OF OBESITY

肥胖症在比喻上和字面上都是一种巨大的疾病。 男性体脂分布的女性表现出夸大的 肥胖的二次健康后果，如增加患肥胖症的可能性 心血管疾病、中风、非胰岛素依赖型糖尿病和 癌症。对人类肥胖的传统动物模型的研究有 在我们对身体潜在机制的认识上留下了相当大的空白 脂肪的分布和沉积。已经有人提出，物种 显示自然发生的身体和脂类循环的变化可能是 在肥胖症研究中具有重要价值。西伯利亚仓鼠 太阳大猩猩)就是这样一个物种。在漫长的夏日般的光周期中，它们是 自然肥胖；然而，当他们被转移到短小的，冬天般的 在光周期中，它们会失去体重，几乎完全是作为身体脂肪。之后 长时间短日暴露和/或日长增加，身体和 脂肪质量增加到他们以前的肥胖状态。因此，这是一个 可逆的，自然发生的肥胖，便于研究，因为 它完全在白天的控制之下。总的目的 这项拟议的研究的目的是检查光周期诱导的 区域脂肪垫在脂肪储存中的特异性变化及其过程 有助于体脂总量的季节性“调节”。 此外，这一规定对能量平衡(即粮食)的影响 摄入量和产热率)将被检查。三个具体目标是 提出，每个都以一套实验为代表。具体目标1：是 总体脂的光周期变化及其调节机制 是这一过程的基础吗？人体脂肪水平将被操纵，以查看是否 对这些挑战进行了季节性适当的调整。体脂 能量输入中的代偿、神经和激素影响及变化 并对产出进行评估。具体目标2：什么荷尔蒙或 自分泌/旁分泌因子介导机体的光周期调控 脂质量、脂代谢和能量平衡？几种激素或 将检测受光周期影响的自分泌/旁分泌因子。 对身体和脂肪质量(脂肪分布)、脂肪的影响 新陈代谢和能量平衡。具体目标3：联合国的作用是什么？ 交感神经系统(SNS)在光周期控制中的作用 脂肪质量，脂肪代谢，能量平衡？的类型和范围 白色脂肪组织(WAT)的神经支配将使用 神经束追踪技术。神经支配的确认和测试 它的功能将通过选择性外科去神经来完成。 控制脂肪分解的光周期诱导的区域特异性变化 (脂肪分解)将被检查，并将包括 脂肪细胞肾上腺素能受体、去甲肾上腺素变化的测定 周转率、体内和体外脂解率。这是一个多学科的 方法应该提供有关光周期影响的新信息 对身体和脂肪质量、脂代谢和能量平衡的影响 反映开发、维护和逆转的基本过程 肥胖症。

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.