Mesenchymal and Neural Regulation of Metabolic Networks
代谢网络的间充质和神经调节
基本信息
- 批准号:10246808
- 负责人:
- 金额:$ 227.57万
- 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:2017-09-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccelerationAddressAdipocytesAdipose tissueAdrenergic beta-AgonistsAffectAgingAnatomyAnimalsAntipsychotic AgentsAreaAutomobile DrivingBMP7 geneBehavioral SymptomsBiochemical PathwayBiologyBiomedical EngineeringBone MarrowBone Morphogenetic ProteinsBone TissueBrainBrain regionBrown FatCell CommunicationCellsCellular biologyCenters of Research ExcellenceChronic DiseaseClinical ResearchCollaborationsCore FacilityCountryDataDevelopmentDiseaseEconomic BurdenEnergy MetabolismEnsureEquipmentExperimental ModelsFatty acid glycerol estersFractureGoalsHealthHealthcare SystemsHistopathologyHumanInvestigationInvestmentsLeadLeadershipLeukocytesLinkLocationMaineMarrowMediatingMedical centerMentorshipMesenchymalMesenchymal Stem CellsMetabolicMetabolic Bone DiseasesMetabolic DiseasesMetabolismMethodologyMolecularNervous system structureNeuraxisNeuronsNursing HomesNutritionalObesityOsteocytesOsteoporosisPatientsPharmaceutical PreparationsPhenotypePhysiologicalPhysiologyPilot ProjectsPlayPrevention programProteomicsRegulationResearch InstituteResearch MethodologyResearch PersonnelRisperidoneRoleSignal PathwaySignal TransductionSignaling ProteinSkeletonStressSympathetic Nervous SystemTechnologyTemperatureTestingThermogenesisTissuesTranslational ResearchUnited StatesWNT Signaling PathwayWeight GainWorkadipocyte differentiationatypical antipsychoticbasebody systembonebone lossbone metabolismbrain tissuecareercircadiancold temperaturecomorbidityembryonic stem cellenergy balancefatty acid oxidationfracture riskhuman diseasehuman population studyhuman studyin vivoinduced pluripotent stem cellinnovationinsightlipid biosynthesislipidomicsmetabolic phenotypemouse modelneuroregulationneurotransmissionnovelobesity treatmentosteoprogenitor cellprogramsprotective effectpsychiatric symptomside effectskeletalstem cellssuccesstreatment program
项目摘要
Whole body metabolism is regulated by the integration of multiple organ systems, including adipose tissue, the
skeleton, and bone marrow. Imbalance in the regulation of these tissues leads to chronic disorders such as
obesity and osteoporosis. Adipocytes and osteoprogenitor cells share a common mesenchymal precursor, and
link these two highly prevalent diseases. Mesenchymal progenitors are also tightly regulated during aging,
nutritional stress, and rapid temperature shifts. There is growing appreciation that the sympathetic nervous
system plays a unique role in this metabolic regulation, both in health and in disease states. Our overall
program goal is to define specific molecular and signaling pathways that integrate the brain, bone, and adipose
tissue in regulation of metabolic networks. This COBRE program, led by Drs. Lucy Liaw and Clifford Rosen,
brings together four projects that test complementary aspects of adipocyte and skeletal metabolic function, and
their regulation by central nervous system input. Project 1 (A. Brown) will study the role of BMP signaling in
brown adipogenesis and thermogenesis, and will optimize thermogenic capacity in human iPS-derived brown
adipocytes by modifying BMP signaling. This project has high translational significance in relation to obesity
and its related co-morbidities. Project 2 (M. Reagan) addresses the origin and function of bone marrow
adipose tissue, a unique depot that is enhanced in osteoporosis and obesity, and may contribute to skeletal
fragility. This project will test the novel hypothesis that osteocyte-derived sclerostin promotes marrow
adipogenesis via inhibition of Wnt signaling, and will utilize bioengineering approaches and mouse models of
altered bone physiology. Project 3 (C. Duarte) is a translational project addressing the consequences of
atypical antipsychotics on bone fracture risk. Atypical antipsychotics such as risperidone (RIS) are highly
prescribed for psychiatric and behavioral symptoms, and have side effects that include bone loss, increased
fracture risk, and weight gain. This project will study nursing home residents, including prevalent users of RIS
and β-blockers, which alone show a protective effect on bone loss in animal studies. This project will determine
if the combination of RIS and β-blockers reduce the risk of fracture compared to RIS alone. Project 4 (K.
Motyl) is complementary to Project 3, and uses mouse models to test the novel hypothesis that RIS acts on
the central nervous system to target bone loss directly or via activation of brown adipose tissue. This project
proposes novel analyses of RIS in brain regions that innervate bone, and also tests the hypothesis that RIS-
induced activation of brown adipose tissue can, in turn, mediate bone loss. These projects will be supported by
an Administrative and Professional Development Core that emphasizes scientific collaboration and continued
professional development, and three scientific cores: (i) Proteomics and Lipidomics Core (C. Vary), (ii)
Histopathology and Histomorphometry Core (V. Lindner), and (iii) Physiology Core for the
Mesenchymal and Neural Regulation of Metabolic Networks COBRE (C. Rosen).
全身代谢受多个器官系统的整合调节,包括脂肪组织,
骨骼和骨髓这些组织调节的不平衡导致慢性疾病,
肥胖症和骨质疏松症。脂肪细胞和骨祖细胞共享共同的间充质前体,
将这两种流行病联系起来间充质祖细胞在衰老过程中也受到严格调控,
营养压力和快速的温度变化。越来越多的人认识到,
系统在这种代谢调节中发挥着独特的作用,无论是在健康还是在疾病状态下。我们的整体
该项目的目标是确定整合大脑、骨骼和脂肪的特定分子和信号通路
组织在调节代谢网络中的作用。这个由露西·廖博士和克利福德·罗森博士领导的COBRE项目,
汇集了四个项目,测试脂肪细胞和骨骼代谢功能的互补方面,
通过中枢神经系统的输入进行调节。项目1(A. Brown)将研究BMP信号在
棕色脂肪生成和产热,并将优化人类iPS衍生棕色脂肪的产热能力。
通过改变BMP信号传导。这个项目在肥胖症方面具有很高的转化意义
及其相关的并发症。项目2(M.里根)地址的起源和功能的骨髓
脂肪组织是一种独特的储存库,在骨质疏松症和肥胖症中得到增强,
脆弱该项目将测试新的假设,即骨细胞衍生的硬化素促进骨髓
脂肪形成通过抑制Wnt信号传导,并将利用生物工程方法和小鼠模型,
改变了骨骼生理学项目3(C. Duarte)是一个翻译项目,
非典型抗精神病药物对骨折风险的影响。非典型抗精神病药,如利培酮(RIS),
处方精神和行为症状,并有副作用,包括骨质流失,增加
骨折风险和体重增加。这个项目将研究疗养院的居民,包括RIS的普遍用户
和β-受体阻滞剂,在动物研究中单独使用它们对骨丢失有保护作用。该项目将决定
如果与单独使用RIS相比,RIS和β受体阻滞剂联合使用可降低骨折风险。项目4(K.
Motyl)是项目3的补充,并使用小鼠模型来测试RIS作用于
中枢神经系统直接或通过激活棕色脂肪组织来瞄准骨质流失。这个项目
提出了新的分析RIS的大脑区域,支配骨骼,也测试假设,RIS-
棕色脂肪组织的诱导活化又可介导骨损失。这些项目将得到以下方面的支持:
一个行政和专业发展核心,强调科学合作,并继续
专业发展和三个科学核心:(i)蛋白质组学和脂质组学核心(C。(ii)
组织学和组织形态学核心(V. Lindner),以及(iii)
代谢网络的间充质和神经调节COBRE(C。罗森)。
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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Lucy Liaw其他文献
Lucy Liaw的其他文献
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{{ truncateString('Lucy Liaw', 18)}}的其他基金
Enhancing research training for Maine Track / Tufts medical students
加强缅因田径/塔夫茨医学院学生的研究培训
- 批准号:
10555468 - 财政年份:2023
- 资助金额:
$ 227.57万 - 项目类别:
Regulation of arterial phenotype by perivascular adipose tissue in cardiometabolic disease
心脏代谢疾病中血管周围脂肪组织对动脉表型的调节
- 批准号:
9495408 - 财政年份:2018
- 资助金额:
$ 227.57万 - 项目类别:
Regulation of arterial phenotype by perivascular adipose tissue in cardiometabolic disease
心脏代谢疾病中血管周围脂肪组织对动脉表型的调节
- 批准号:
9977874 - 财政年份:2018
- 资助金额:
$ 227.57万 - 项目类别:
Regulation of arterial phenotype by perivascular adipose tissue in cardiometabolic disease
心脏代谢疾病中血管周围脂肪组织对动脉表型的调节
- 批准号:
10443027 - 财政年份:2018
- 资助金额:
$ 227.57万 - 项目类别:
Regulation of arterial phenotype by perivascular adipose tissue in cardiometabolic disease
心脏代谢疾病中血管周围脂肪组织对动脉表型的调节
- 批准号:
10231190 - 财政年份:2018
- 资助金额:
$ 227.57万 - 项目类别:
Regulation of arterial phenotype by perivascular adipose tissue in cardiometabolic disease
心脏代谢疾病中血管周围脂肪组织对动脉表型的调节
- 批准号:
10610480 - 财政年份:2018
- 资助金额:
$ 227.57万 - 项目类别:
COBRE in Mesenchymal and Neural Regulation of Metabolic Networks - Metabolic Phenotyping Equipment
COBRE 在代谢网络的间充质和神经调节中的作用 - 代谢表型设备
- 批准号:
10396172 - 财政年份:2017
- 资助金额:
$ 227.57万 - 项目类别:
Lewy Body Dementia and Alpha Synuclein Induced Changes in Adipose Tissue
路易体痴呆和α突触核蛋白引起脂肪组织的变化
- 批准号:
10117901 - 财政年份:2017
- 资助金额:
$ 227.57万 - 项目类别:
Core A: Administrative and Professional Development Core
核心 A:行政和专业发展核心
- 批准号:
10246818 - 财政年份:2017
- 资助金额:
$ 227.57万 - 项目类别:
Phase II COBRE in Mesenchymal and Neural Regulation of Metabolic Networks
COBRE 代谢网络间充质和神经调节的 II 期研究
- 批准号:
10711692 - 财政年份:2017
- 资助金额:
$ 227.57万 - 项目类别:
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