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.

肥胖是西方最普遍的营养问题

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