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展，然而， 一些基本问题仍然没有答案。目前认为， 脂肪组织中的“临界”脂肪细胞大小（FCS）刺激增加 脂肪细胞数（FCN）。这种脂肪细胞增殖的假设 从来没有被证明，也没有实验证明， 这一过程所涉及的机制或因素。再者是 很可能引发增殖的“临界”脂肪细胞大小可能 在不同的肥胖模型中有所不同，而且，从脂肪库到 仓库。 因此，本研究计划的总体目标是测试 脂肪细胞增殖的刺激是由于 现有的脂肪细胞达到临界脂质储存能力， 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（“脂肪形成因子”[AF]）是否 负责增加脂肪细胞数量。人类的三种模式 将检查两种测试模型：l）遗传诱导的肥胖： Zucker fat/fat rats; 2）伴随老年的自发性肥胖： Wistar大鼠; 3）饮食诱导的肥胖：高脂饮食（HFD）喂养Wistar大鼠 大鼠; 4）季节性（光周期）诱导的肥胖：叙利亚仓鼠;和5） 增生模型：豚鼠。使用独特的方法和结合 研究人员的专业知识，每个定义的模型将是 研究分三个阶段：l）活性脂肪细胞的鉴定 增殖状态; 2）增殖和分化的检测 活动的全身和局部AF的时间间隔之前，期间和 在第1阶段确定的临界增殖状态之后。可能 将研究脂肪组织代谢与AF的联系。3)测试 规律饮食延缓脂肪细胞大小成熟假说 限制将导致延迟的增殖活性和延迟的 AF的表达。 将使用从五个动物模型中的每一个收集的信息 回答四个具体目标中提出的问题。（一）A 关键FCS导致脂肪细胞增殖？2)是扩散和 脂肪组织中脂肪细胞的分化与 局部或全身性房颤的产生？3)自分泌/旁分泌 脂肪组织中存在的因子，是否有任何一个可能与 FCS和脂肪生成活性，从而具有AF的特征？ 4)组成脂肪组织的变化或代谢事件是否会触发 在肥胖症发展过程中出现房颤？ 这些研究将有助于了解 肥胖的发展，并可能提出可能的方法，以防止或阻止 脂肪细胞增殖