FAT CELL PROLIFERATION IN OBESITY--MODULATING FACTORS

肥胖症中的脂肪细胞增殖——调节因素

• 批准号: 2518348
• 负责人: Roy Joseph Martin
• 金额: $ 29.89万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518348
• 关键词: adipocytes; adipose tissue; biological models; cell cycle; cell differentiation; cell morphology; dietary lipid; glucose metabolism; growth factor; growth media; guinea pigs; hamsters; hyperplasia; hypertrophy; insulinlike growth factor; laboratory rat; lipolysis; lipoprotein lipase; nutrition related tag; obesity; prostaglandins; reducing diet; tissue /cell culture

Obesity is the most prevalent nutritional problem in western civilization. Much progress has been made in the last 30 years, yet, basic questions remain unanswered. It is currently believed that reaching a "critical" fat cell size (FCS) in adipose tissue stimulates increases in fat cell number (FCN). This hypothesis of fat cell proliferation has never been proven and there are no experiments that demonstrate the mechanisms or the factors involved in this process. Furthermore, it is likely that the "critical" fat cell size that triggers proliferation may vary in different models of obesity, and, also from adipose depot to depot. Therefore, the overall goals of this research plan are to test whether the stimulation of fat cell proliferation is due to a consequence of existing fat cells reaching a critical lipid storage capacity, and to determine the mechanisms that underlie fat cell proliferation in obesity. To accomplish these goals, we will test several obesity models to determine if a local or systemic substance ("adipogenic factor" [AF]) is responsible for increases in fat cell number. Three models of human obesity and two test models will be examined: l) genetic-induced obesity: Zucker fat/fat rats; 2) spontaneous obesity that accompanies old age: Wistar rats; 3) diet-induced obesity: high fat diet (HFD)-fed Wistar rats; 4) seasonal (photoperiod)-induced obesity: Syrian hamsters; and 5) hyperplastic model: Guinea pig. Using a unique approach and the combined expertise of the investigators, each of the defined models will be studied in three stages: l) Identification of an active fat cell proliferative state; 2) Testing for proliferative and differentiative activity of systemic and local AFs at time intervals before, during and after the critical proliferative state identified in Stage 1. Possible adipose tissue metabolic links with AF will be studied. 3) Testing the hypothesis that delaying fat cell size maturation by scheduled food restriction will result in delayed proliferative activity and delayed expression of AFs. The information gathered from each of the five animal models will be used to answer the questions posed in the four specific aims. I) Does a critical FCS lead to fat cell proliferation? 2) Is the proliferation and differentiation of fat cells in adipose tissue associated with the production of a local or systemic AF? 3) Of the known autocrine/paracrine factors present in adipose tissue, is there any one that may be related to FCS and adipogenic activity thus having the characteristics of an AF? 4) Do compositional adipose tissue changes or metabolic events trigger the appearance of the AF during the development of obesity? These studies will help the understanding of the fundamentals of the development of obesity and may suggest possible ways to prevent or arrest fat cell proliferation.

肥胖是西方最普遍的营养问题。 文明。在过去的30年里取得了很大的进步，然而， 基本的问题仍然没有得到回答。目前人们认为，到达 脂肪组织中“临界”脂肪细胞大小(FCS)刺激增加 以脂肪细胞数(FCN)表示。这一脂肪细胞增殖假说具有 从未被证实过，也没有实验可以证明 机制或这一过程中涉及的因素。此外，它是 很可能触发增殖的“临界”脂肪细胞大小可能 在不同的肥胖模型中，也有不同的脂肪仓库 车辆段。 因此，这项研究计划的总体目标是测试 刺激脂肪细胞增殖是由于 现有脂肪细胞达到临界脂肪存储能力，并 确定肥胖症中脂肪细胞增殖的机制。 为了实现这些目标，我们将测试几种肥胖模型 确定局部或全身物质(“成脂因子”[AF])是否 负责脂肪细胞数量的增加。人类的三个模型 肥胖和两个测试模型：L)遗传性肥胖： Zucker胖/胖大鼠；2)伴随着老年的自发性肥胖： Wistar大鼠；3)饮食诱导肥胖：高脂饮食喂养的Wistar大鼠 大鼠；4)季节性(光周期)诱导的肥胖：叙利亚仓鼠；和5) 增生症模型：豚鼠。使用一种独特的方法和组合 调查人员的专业知识，每个已定义的模型将 研究分三个阶段：L)活性脂肪细胞的鉴定 增殖状态；2)增殖和分化试验 全身性和局部AFS在活动前、期间和期间的活动 在阶段1中确定的临界增殖状态之后。可能 脂肪组织代谢与房颤的联系将被研究。3)测试 通过预定食物延缓脂肪细胞大小成熟的假说 限制将导致延迟的增殖活动和延迟 AFS的表达。 从五个动物模型中收集的信息将被使用 回答四个具体目标中提出的问题。I)做一个 关键的FCS导致脂肪细胞增殖？2)是脂肪细胞的增殖和 脂肪组织中脂肪细胞的分化与 产生已知的局部或全身性自分泌/旁分泌 脂肪组织中存在的因素，有没有可能与 对FCS和成脂活性从而具有房颤的特征？ 4)成分脂肪组织改变或代谢事件是否会引发 在肥胖的发展过程中房颤的出现？ 这些研究将有助于理解 肥胖的发展，并可能提出预防或遏制肥胖的可能方法 脂肪细胞增殖。