The roles of Gdf3 in adipogenesis and adipocyte function

Gdf3 在脂肪生成和脂肪细胞功能中的作用

基本信息

批准号：
7094934
负责人：
Chester W Brown
金额：
$ 7.5万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2008-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Overweight and obesity are growing problems worldwide. Obesity is a tremendous health burden for the U.S. with estimates of >10% of health care expenditures devoted annually to the problem, due to morbidity from its associated conditions. Moreover, this is an alarming issue in the Pediatrics population. A recent estimate indicates that 15.5% of American children currently overweight or obese, doubling in the past 2 decades, with even higher rates among minority and economically disadvantaged groups. While socioeconomic and cultural factors clearly play an important role, the genetics of obesity is now being dissected and several genes are now implicated in the susceptibility to this disorder. Understanding mechanisms by which these genes exert their effects on body fat composition may provide important clues that will aid in developing new strategies to aid in the war on obesity and its co-morbid conditions. Growth differentiation factor 3 (Gdf3) is a member of the TGF-b superfamily, expressed in adipose. We have generated mice with a homozygous null mutation of this gene. When maintained on a high fat diet, these knockout mice exhibit resistance to obesity, suggesting a possible role in adipocyte differentiation and/or function. This proposal aims to study this phenomenon further, potentially leading to pharmacologic interventions to help combat this disease. The specific aims of this proposal are 1) to further define which cell types within white adipose tissue express GDF3 2) to assess the physiologic and molecular contributors to the increased metabolic rates of Gdf3-/- mice 3) to further examine GDFS's roles in the mature adipocyte.

描述（由申请人提供）：超重和肥胖是世界范围内日益严重的问题。肥胖对美国来说是一个巨大的健康负担，由于相关疾病的发病率，估计每年有超过 10% 的医疗保健支出用于解决肥胖问题。此外，这在儿科人群中是一个令人担忧的问题。最近的一项估计表明，目前有 15.5% 的美国儿童超重或肥胖，这一比例在过去 20 年中翻了一番，少数族裔和经济弱势群体的比例更高。虽然社会经济和文化因素显然发挥着重要作用，但肥胖的遗传学现在正在被剖析，并且现在有几个基因与这种疾病的易感性有关。了解这些基因对身体脂肪成分产生影响的机制可能会提供重要的线索，有助于制定新的策略来帮助对抗肥胖及其并发症。生长分化因子 3 (Gdf3) 是 TGF-b 超家族的成员，在脂肪中表达。我们已经培育出具有该基因纯合无效突变的小鼠。当维持高脂肪饮食时，这些基因敲除小鼠表现出对肥胖的抵抗力，这表明可能在脂肪细胞分化和/或功能中发挥作用。该提案旨在进一步研究这种现象，有可能导致药物干预措施来帮助对抗这种疾病。该提案的具体目的是 1) 进一步确定白色脂肪组织中表达 GDF3 的细胞类型 2) 评估 Gdf3-/- 小鼠代谢率增加的生理和分子因素 3) 进一步检查 GDFS 在成熟的脂肪细胞。