Molecular regulation of adipose tissue development, homeostasis and expansion
脂肪组织发育、稳态和扩张的分子调节
基本信息
- 批准号:10387834
- 负责人:
- 金额:$ 7.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-19 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdipocytesAdipose tissueAdoptedAdultAtherosclerosisCellsChildDataDevelopmentDiabetes MellitusEpidemicFatty acid glycerol estersGap JunctionsGeneticHealthHeart DiseasesHigh Fat DietHomeostasisHypertensionLeadMalignant NeoplasmsMapsMechanicsMetabolicMetabolic DiseasesMolecularMorphogenesisNon-Insulin-Dependent Diabetes MellitusObesityOrganogenesisOverweightPatternPlatelet-Derived Growth FactorPlatelet-Derived Growth Factor alpha ReceptorPopulationPublic HealthRegulationSignal TransductionSourceTissue ExpansionTissuesUnited Statesadult obesitybaseblastomere structurefeedinggene functionmigrationmouse modelnovelobesity in childrenobesogenicprogenitorresponsestem cellstherapeutic targettool
项目摘要
Project Summary
Childhood and adult obesity and their associated metabolic complications is a public health problem. In the
United States alone, more than 67% of adults and 33% of children are currently overweight or obese, which
can cause both immediate and long-term health problems. If this epidemic is uncorrected it will lead to a range
of ensuing metabolic disorders such as heart disease, diabetes, atherosclerosis, and cancer. Adipose or fat
tissues appear to be at the nexus of the obesity crisis. However, very little is known about the cells and
molecular mechanisms that oversee the formation and the expansion of adipocytes and adipose tissues. Our
recent findings using genetic mouse models demonstrate that there are two progenitor populations that give
rise to adipocytes: developmental progenitors, for adipose development, and adult progenitors, for adipose
homeostasis. In established adult adipose depots, not developmental adipose depots, adipocytes fate-map
from a perivascular residing progenitor cell pool. Contrary to adult adipose tissue, even less is known about the
cellular origin of developmental progenitor cells and the signals that control their cellular dynamics including
pattern, proliferation, migration and formation. The central focus of this proposal aims to use our genetic tools
to identify novel regulatory mechanisms important for adipose tissue development compared to adult adipose
tissue homeostasis and expansion. Previous studies have suggested that platelet derived growth factor
receptor α (PDGFRα) is an important potential source of developmental adipose progenitor cells. Furthermore,
PDGFRα+ cells contribute to adipose tissue expansion in respond to high fat diet feeding. However, few
studies have examined if PDGFRα, gene function, is critical for adipose tissue development or adult regulation.
Based on our preliminary data, I hypothesize that PDGFRα signaling is a central regulator of adipose tissue
development by establishing the adipose lineage. Thus the specific aims of this study are focused on: Aim 1:
Determine if PDGFRα is necessary for adipose tissue development (organogenesis). Aim 2: Determine the
mechanisms by which PDGFRα controls adipose tissue development. Aim 3: Determine if PDGFRα is
necessary for adult adipose tissue obesogenic expansion. Based on preliminary data, PDGFRα is critical for
the development of adipose tissue but not for maintaining it. It appears that PDGFRα regulates adipose
progenitor cell fate promoting adipose tissue organogenesis. These findings will be of great importance for
three reasons: 1) how embryonic cells adopt an adipose tissue cell fate, 2) the molecular underpinning that
govern this developmental cell fate, and 3) how adipose tissue expands in response to caloric excess
compared to adult adipose tissue homeostasis. These important findings may lead to novel discrete
therapeutic targets for childhood and adult obesity.
项目摘要
儿童和成人肥胖及其相关的代谢并发症是一个公共卫生问题。在
仅在美国,超过67%的成年人和33%的儿童目前超重或肥胖,
会导致即时和长期的健康问题。如果这种流行病得不到纠正,
随之而来的代谢紊乱,如心脏病、糖尿病、动脉粥样硬化和癌症。脂肪或脂肪
组织似乎是肥胖危机的关键。然而,人们对这些细胞知之甚少,
监督脂肪细胞和脂肪组织的形成和扩张的分子机制。我们
最近使用遗传小鼠模型的研究结果表明,有两个祖先群体,
生成脂肪细胞:发育祖细胞,用于脂肪发育,和成体祖细胞,用于脂肪发育
体内平衡。在已建立的成人脂肪库中,而不是发育中的脂肪库中,脂肪细胞命运图
从血管周围的祖细胞池中分离出来。与成人脂肪组织相反,
发育祖细胞的细胞起源和控制其细胞动力学的信号,包括
模式、扩散、迁移和形成。这项建议的核心重点是利用我们的遗传工具
确定与成人脂肪组织相比,对脂肪组织发育重要的新的调节机制,
组织稳态和扩张。以前的研究表明,血小板衍生生长因子
PDGFRα受体是发育中脂肪祖细胞的重要潜在来源。此外,委员会认为,
PDGFRα+细胞有助于脂肪组织扩张,以响应高脂饮食喂养。但很少
研究已经检查了PDGFRα基因功能是否对脂肪组织发育或成人调节至关重要。
基于我们的初步数据,我假设PDGFRα信号是脂肪组织的中心调节因子,
通过建立脂肪谱系进行发育。因此,本研究的具体目标集中在:目标1:
确定PDGFRα是否是脂肪组织发育(器官发生)所必需的。目标2:确定
PDGFRα控制脂肪组织发育的机制。目的3:确定PDGFRα是否
对于成人脂肪组织致胖性扩张是必要的。根据初步数据,PDGFRα对于
PDGFRα调节脂肪组织的生长,而不是维持脂肪组织的生长。
祖细胞命运促进脂肪组织器官发生。这些发现将对
三个原因:1)胚胎细胞如何采用脂肪组织细胞的命运,2)分子基础,
控制着这种发育细胞的命运,以及3)脂肪组织如何响应热量过剩而膨胀
与成人脂肪组织稳态相比。这些重要的发现可能会导致新的离散
儿童和成人肥胖症的治疗目标。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Yuwei Jiang的其他文献
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{{ truncateString('Yuwei Jiang', 18)}}的其他基金
Regulation of beige adipocyte maintenance and its impact on metabolic outcomes
米色脂肪细胞维持的调节及其对代谢结果的影响
- 批准号:
10420996 - 财政年份:2022
- 资助金额:
$ 7.92万 - 项目类别:
Regulation of beige adipocyte maintenance and its impact on metabolic outcomes
米色脂肪细胞维持的调节及其对代谢结果的影响
- 批准号:
10621893 - 财政年份:2022
- 资助金额:
$ 7.92万 - 项目类别:
Regulation of adipose lineage plasticity in obesity
肥胖症中脂肪谱系可塑性的调节
- 批准号:
10352438 - 财政年份:2021
- 资助金额:
$ 7.92万 - 项目类别:
Molecular regulation of adipose tissue development, homeostasis and expansion
脂肪组织发育、稳态和扩张的分子调节
- 批准号:
9354184 - 财政年份:2016
- 资助金额:
$ 7.92万 - 项目类别:
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