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: 2905585
• 负责人: Roy Joseph Martin
• 金额: $ 32.34万
• 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 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2905585
• 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.

肥胖是西方国家最普遍的营养问题 文明。过去 30 年取得了很大进展，但 基本问题仍未得到解答。目前认为达到 脂肪组织中的“临界”脂肪细胞大小（FCS）会刺激增加 脂肪细胞数（FCN）。这种脂肪细胞增殖的假说 从未被证明，也没有实验证明 该过程涉及的机制或因素。此外，它是 触发增殖的“临界”脂肪细胞大小可能 不同的肥胖模型有所不同，并且脂肪库和 仓库。 因此，本研究计划的总体目标是测试是否 刺激脂肪细胞增殖是由于 现有的脂肪细胞达到临界脂质储存能力，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（“脂肪形成因子”[AF]）是否 负责脂肪细胞数量的增加。人类的三种模型 将检查肥胖和两个测试模型：l) 遗传性肥胖： Zucker脂肪/肥胖大鼠； 2）伴随老年而来的自发性肥胖： 威斯塔鼠； 3）饮食引起的肥胖：高脂饮食（HFD）喂养的Wistar 老鼠； 4）季节性（光周期）引起的肥胖：叙利亚仓鼠；和 5) 增生模型：豚鼠。使用独特的方法和组合 研究人员的专业知识，每个定义的模型将 分三个阶段进行研究： l) 活性脂肪细胞的鉴定 增殖状态； 2) 增殖和分化测试 之前、期间和期间的时间间隔内的全身和局部 AF 活动 在第一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 通过定期食物延迟脂肪细胞大小成熟的假设 限制将导致增殖活性延迟并延迟 AF 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) 是否 关键FCS导致脂肪细胞增殖？ 2) 是否扩散和 脂肪组织中脂肪细胞的分化与 产生局部或全身性房颤？ 3) 已知的自分泌/旁分泌 脂肪组织中存在的因素，是否有任何一项可能与之相关 FCS 和脂肪生成活性因此具有 AF 的特征？ 4) 脂肪组织成分变化或代谢事件是否会触发 肥胖发展过程中房颤的出现？ 这些研究将有助于理解基本原理 肥胖的发展，并可能提出预防或阻止肥胖的可能方法 脂肪细胞增殖。

项目成果

Enhancing effect of troglitazone on porcine adipocyte differentiation in primary culture: a comparison with dexamethasone.

曲格列酮对原代培养猪脂肪细胞分化的增强作用：与地塞米松的比较。

• DOI: 10.1038/oby.2000.85
• 发表时间: 2000
• 期刊: Obesity research
• 作者: Tchoukalova,YD;Hausman,DB;Dean,RG;Hausman,GJ
• 通讯作者: Hausman,GJ

Dietary fat type and level influence adiposity development in obese but not lean Zucker rats.

膳食脂肪类型和水平影响肥胖 Zucker 大鼠的肥胖发展，但不影响瘦 Zucker 大鼠。

• DOI: 10.3181/00379727-218-44265
• 发表时间: 1998
• 期刊: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)
• 作者: Loh,MY;Flatt,WP;Martin,RJ;Hausman,DB
• 通讯作者: Hausman,DB

The biology of white adipocyte proliferation.

• DOI: 10.1046/j.1467-789x.2001.00042.x
• 发表时间: 2001-11-01
• 期刊: Obesity reviews : an official journal of the International Association for the Study of Obesity
• 作者: Hausman, D B;DiGirolamo, M;Martin, R J
• 通讯作者: Martin, R J

Adipocyte development is dependent upon stem cell recruitment and proliferation of preadipocytes.

脂肪细胞的发育取决于干细胞的募集和前脂肪细胞的增殖。

• DOI: 10.1002/j.1550-8528.1999.tb00438.x
• 发表时间: 1999
• 期刊: Obesity research
• 作者: Kras,KM;Hausman,DB;Hausman,GJ;Martin,RJ
• 通讯作者: Martin,RJ

Photoperiod and gender affect adipose tissue growth and cellularity in juvenile Syrian hamsters.

光周期和性别影响幼年叙利亚仓鼠的脂肪组织生长和细胞结构。

• DOI: 10.1016/s0031-9384(00)00364-4
• 发表时间: 2000
• 期刊: Physiology & behavior
• 影响因子: 2.9
• 作者: Plunkett,SS;Fine,JB;Bartness,TJ
• 通讯作者: Bartness,TJ