Adipocyte metabolism and stem cell lineage responses
脂肪细胞代谢和干细胞谱系反应
基本信息
- 批准号:10004144
- 负责人:
- 金额:$ 32.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-05 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdenosineAdipocytesAffectAmino AcidsBiological ProcessBody partCell CountCell Differentiation processCell LineageCell SurvivalCoupledDataDaughterDietDiseaseDrosophila genusDrug PrescriptionsDrug TargetingEnzymesG Protein-Coupled Receptor SignalingG-Protein-Coupled ReceptorsGTP-Binding ProteinsGoalsHematopoiesisHomologous GeneHormonesHumanImmunityInsulinLinkMacronutrients NutritionMalignant NeoplasmsMeasuresMetabolicMetabolic DiseasesMetabolic PathwayMetabolismNutrientObesityOrganOrganismOvaryPathway interactionsPhenotypePhysiologicalProcessPurinergic P1 ReceptorsResearchRiskRoleSignal PathwaySignal TransductionSirolimusTestingWestern WorldWorkadult stem cellcancer cellextracellulargermline stem cellsin vivoinsightknock-downreceptorreceptor-mediated signalingresponseself-renewalstemstem cell fatestem cell modelstem cellssteroid hormonetissue stem cellstool
项目摘要
Project Summary:
Nutrients affect tissue stem cell lineages in all organisms. Interorgan signaling allows the impact of diet or
physiological factors on one organ to be communicated to stem cell lineages elsewhere. Circulating levels of
most energy substrates and metabolites vary with diet, and many of these activate G protein coupled receptors
(GPCRs), which are associated with metabolic diseases, cancers and other disorders. It is therefore essential
to investigate how GPCR signaling links metabolism to stem lineage processes in vivo. Adipocytes have key
metabolic roles, and obesity increases the risk for many diseases. Among them are cancers, which share
similarities with stem cells. Signaling pathways that control normal stem cells are often deregulated in cancers
(e.g. diet-dependent pathways), and cancers and stem cells have large proliferative potential and generate
differentiated cells in deregulated or controlled ways, respectively. The goal of this proposal is to study how
diet controls adipocyte metabolism and how GPCR signaling mediates its effects on stem cell lineages using
the Drosophila germline stem cell (GSC) model. Drosophila has highly conserved adipocyte metabolism and
well characterized stem cells. One can readily identify GSCs and quantify self-renewal, proliferation,
differentiation and survival along their lineage. GSCs and their progeny divide and grow faster on a rich diet,
partially via insulin, steroid hormone, and Target of Rapamycin (TOR) signaling in the ovary. Adipocytes
contribute to the GSC response to diet, as adipocyte-specific disruption of amino acid transport or TOR causes
distinct GSC lineage phenotypes. Our unpublished data show that diet also regulates metabolic pathways in
adipocytes, and key adipocyte enzymes influence GSC number, proliferation, and differentiation, survival of
their daughters. In addition, our results show that distinct G proteins regulate GSC fate and division, and
progeny survival, suggesting that GPCR signaling actively modulates the GSC lineage. We will test our
hypothesis that key diet-dependent metabolic pathways in adipocytes control the levels of metabolites (or other
downstream factors) that act directly on the ovary (or indirectly, through intermediate organs) to modulate the
GSC lineage through the following aims: 1) To determine how macronutrients and diet-dependent hormones
impact key adipocyte metabolic pathways; and 2) To probe the role of G protein coupled receptor (GPCR)
signaling in the GSC lineage. Relevance: Obesity is prevalent in the western world and results in the abnormal
function of fat cells, which in turn increases the risk for many diseases, including cancers. We propose to take
advantage of powerful research tools in fruitflies to investigate how metabolic processes in fat cells normally
generate signals that affect the function of stem cells in other parts of the body. Because of the high degree of
evolutionary conservation of molecules and biological processes between fruitflies and humans, this work will
likely provide valuable insights into diseases resulting from metabolic abnormalities in fat cells.
项目总结:
营养物质会影响所有生物体的组织干细胞谱系。器官间信号传递允许饮食或
一个器官上的生理因素被传递到其他地方的干细胞谱系。循环中的水平
大多数能量底物和代谢物因饮食不同而不同,其中许多激活了G蛋白偶联受体
(GPCRs),这与代谢性疾病、癌症和其他疾病有关。因此,它是必不可少的
研究GPCR信号如何将新陈代谢与体内的干细胞谱系过程联系起来。脂肪细胞有钥匙
代谢作用,肥胖增加了许多疾病的风险。其中包括癌症,它们共同
与干细胞有相似之处。控制正常干细胞的信号通路在癌症中经常被解除调控
(例如,饮食依赖的途径),癌症和干细胞具有巨大的增殖潜力并产生
分别以解除调控或控制的方式分化细胞。这项提案的目标是研究如何
饮食控制脂肪细胞代谢以及GPCR信号如何介导其对干细胞谱系的影响
果蝇生殖系干细胞(GSC)模型果蝇具有高度保守的脂肪细胞代谢和
干细胞的特性很好。人们可以很容易地识别GSC并量化自我更新、增殖
沿着它们的谱系分化和生存。GSCs及其后代在丰富的饮食中分裂和生长更快,
部分通过胰岛素、类固醇激素和卵巢中的雷帕霉素靶点(TOR)信号传递。脂肪细胞
促进GSC对饮食的反应,因为脂肪细胞特异性的氨基酸运输中断或TOR引起
不同的GSC血统表型。我们未发表的数据表明,饮食也调节新陈代谢途径。
脂肪细胞和关键的脂肪细胞酶影响GSC的数量、增殖、分化和存活
他们的女儿。此外,我们的结果表明,不同的G蛋白调节GSC的命运和分裂,并且
子代存活,表明GPCR信号积极地调节GSC谱系。我们将测试我们的
假设脂肪细胞中依赖饮食的关键代谢途径控制代谢物(或其他
下游因子)直接作用于卵巢(或通过中间器官间接作用),以调节
GSC谱系通过以下目标:1)确定大量营养素和饮食依赖激素
影响脂肪细胞代谢的关键途径;2)探讨G蛋白偶联受体的作用
GSC血统中的信号。相关性:肥胖在西方世界很普遍,并导致不正常的
脂肪细胞的功能,这反过来增加了许多疾病的风险,包括癌症。我们建议采取
利用果蝇强大的研究工具研究脂肪细胞的正常代谢过程
产生影响身体其他部位干细胞功能的信号。因为高度的
果蝇和人类之间分子和生物过程的进化守恒,这项工作将
可能对脂肪细胞代谢异常引起的疾病提供有价值的见解。
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Analysis of Gal4 Expression Patterns in Adult Drosophila Females.
- DOI:10.1534/g3.120.401676
- 发表时间:2020-11-05
- 期刊:
- 影响因子:0
- 作者:Weaver LN;Ma T;Drummond-Barbosa D
- 通讯作者:Drummond-Barbosa D
Chronic exposure to warm temperature causes low sperm abundance and quality in Drosophila melanogaster.
- DOI:10.1038/s41598-023-39360-7
- 发表时间:2023-07-30
- 期刊:
- 影响因子:4.6
- 作者:Gandara, Ana Caroline P.;Drummond-Barbosa, Daniela
- 通讯作者:Drummond-Barbosa, Daniela
RNAi-based screens uncover a potential new role for the orphan neuropeptide receptor Moody in Drosophila female germline stem cell maintenance.
- DOI:10.1371/journal.pone.0243756
- 发表时间:2020
- 期刊:
- 影响因子:3.7
- 作者:Ma T;Matsuoka S;Drummond-Barbosa D
- 通讯作者:Drummond-Barbosa D
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Daniela Drummond-Barbosa其他文献
Daniela Drummond-Barbosa的其他文献
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{{ truncateString('Daniela Drummond-Barbosa', 18)}}的其他基金
Nutrient fuel preference, obesity, and stem cell lineage physiology
营养燃料偏好、肥胖和干细胞谱系生理学
- 批准号:
10635071 - 财政年份:2021
- 资助金额:
$ 32.75万 - 项目类别:
Nutrient fuel preference, obesity, and stem cell lineage physiology
营养燃料偏好、肥胖和干细胞谱系生理学
- 批准号:
10665801 - 财政年份:2021
- 资助金额:
$ 32.75万 - 项目类别:
Nutrient fuel preference, obesity, and stem cell lineage physiology
营养燃料偏好、肥胖和干细胞谱系生理学
- 批准号:
10165881 - 财政年份:2021
- 资助金额:
$ 32.75万 - 项目类别:
Molecular Mechanisms of Meiotic Maturation in Drosophila
果蝇减数分裂成熟的分子机制
- 批准号:
8288746 - 财政年份:2005
- 资助金额:
$ 32.75万 - 项目类别:
Molecular Mechanisms of Meiotic Maturation in Drosophila
果蝇减数分裂成熟的分子机制
- 批准号:
7887289 - 财政年份:2005
- 资助金额:
$ 32.75万 - 项目类别:
alpha-Endosulfine, Insulin,& Adult Tissue Growth Control
α-硫磺、胰岛素、
- 批准号:
7065358 - 财政年份:2005
- 资助金额:
$ 32.75万 - 项目类别:
Nutrient Sensing in Adipocytes and the Control of Oogenesis in Drosophila
脂肪细胞的营养感应和果蝇卵子发生的控制
- 批准号:
8758798 - 财政年份:2005
- 资助金额:
$ 32.75万 - 项目类别:
alpha-Endosulfine, Insulin,& Adult Tissue Growth Control
α-硫磺、胰岛素、
- 批准号:
7035768 - 财政年份:2005
- 资助金额:
$ 32.75万 - 项目类别:
Nutrient Sensing in Adipocytes and the Control of Oogenesis in Drosophila
脂肪细胞的营养感应和果蝇卵子发生的控制
- 批准号:
8908016 - 财政年份:2005
- 资助金额:
$ 32.75万 - 项目类别:
alpha-Endosulfine, Insulin,& Adult Tissue Growth Control
α-硫磺、胰岛素、
- 批准号:
7614326 - 财政年份:2005
- 资助金额:
$ 32.75万 - 项目类别:
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