Development and validation of a human brown adipocyte system
人类棕色脂肪细胞系统的开发和验证
基本信息
- 批准号:8904122
- 负责人:
- 金额:$ 22.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-03-01 至 2016-02-29
- 项目状态:已结题
- 来源:
- 关键词:AddressAdipocytesAdipose tissueAdultAffectAgeBenchmarkingBiological AssayBiological MarkersBiological ModelsBiologyBody Weight decreasedBrown FatBurn injuryCell Culture SystemCell LineCell modelCellsCommunitiesComorbidityDataDevelopmentDiseaseDrug TargetingEnergy MetabolismEpidemicFeasibility StudiesFetal TissuesGenderGenerationsGeneticGoalsHeatingHumanHuman IdentificationsIncidenceInfantKnowledgeLeadLocationLongevityMeasuresMediatingMetabolicMetabolic DiseasesMitochondriaModalityModelingNon-Insulin-Dependent Diabetes MellitusObesityObesity associated diseaseOxidative PhosphorylationPathway interactionsPerformancePhasePlasmaPopulationPrevalenceProceduresProductionProtocols documentationProviderQuality ControlResearchResearch PersonnelRespirationRodentRodent ModelStimulusSystemTargeted ResearchTestingTherapeuticThermogenesisTissuesTriglyceridesUnited StatesValidationadipocyte differentiationcomparativedemographicsdiabeticexperiencefatty acid oxidationfetalfight againstfunctional genomicshigh throughput screeningimmortalized celllipid biosynthesisnovelnovel therapeutic interventionnovel therapeuticsobesity treatmentoxidationphase 1 studypublic health relevancescreeningtherapeutic targettool
项目摘要
DESCRIPTION (provided by applicant): The activation and recruitment of brown adipose tissue has become an exciting target in the fight against obesity and its related metabolic diseases. Brown adipose tissue differs from white adipose tissue in its critical ability to burn energy as heat through UCP-1 driven adaptive thermogenesis. Expression of mitochondrial UCP-1 uncouples oxidative phosphorylation, resulting in accelerated substrate oxidation but low ATP production. The resulting dissipation of energy is associated with plasma triglyceride clearance, a key factor in weight loss. The brown adipose depot has long been known to exist in rodents as well as in human infants. However, recent evidence has demonstrated the existence of active brown adipose tissue in human adults. These findings prompted a resurgence of research focusing on both the activation of brown adipose tissue and the "browning" of white adipose tissue, a phenomenon wherein UCP-1-mediated mitochondrial uncoupling is induced by stimuli. Studies using rodent models have demonstrated that brown fat activation or induction of browning can promote beneficial metabolic effects, and promising therapeutic targets have been identified. However, the therapeutic potential of these targets has not been confirmed due to the lack of a widely available human brown adipocyte model. Therefore, there is a pronounced need to validate existing therapeutic targets in the human system. ZenBio will address this need by providing both a primary and immortalized human brown adipocyte cell culture system to the research community and will utilize these tools to establish a screen to identify activators of human brown adipogenesis. The principal goal of this project is to generate and characterize a human adult brown adipocyte cell system. We will achieve this in a stepwise fashion, beginning with an initial feasibility study focused on human fetal brown adipocytes. Aim I will use functional and genomic analyses to generate a widely available fetal brown adipocyte model which will be used as a tool to establish the adult cell system. The fetal model will be developed first due to the comparative ease of detecting fetal brown adipose tissue and its ready availability through existing procurement agencies. The second aim is to generate and characterize an immortalized fetal brown adipocyte system for high throughput/high content screening. These cells will circumvent the limited material and lifespan of primary cells and allow for the development of a high throughput screening platform to identify novel targets of brown adipocyte activation. Phase I will be expanded in Phase II with the goal of characterizing and commercializing the human adult brown adipocyte system from donors of differing BMI, age, gender and diabetic state. These studies will generate both primary and immortalized human adult adipocyte cells which will be used to identify novel targets of brown adipocyte energy expenditure for the treatment of obesity.
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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YOLANDA Renee LEA-CURRIE其他文献
YOLANDA Renee LEA-CURRIE的其他文献
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Tuned stem cell extracellular vesicles are a novel chronic wound therapeutic
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Commercialization of a Human Myocyte and Adipocyte Co-Culture System
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- 批准号:
7611887 - 财政年份:2007
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Commercialization of a Human Myocyte and Adipocyte Co-Culture System
人类心肌细胞和脂肪细胞共培养系统的商业化
- 批准号:
7692905 - 财政年份:2007
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Commercialization of a Human Myocyte and Adipocyte Co-Culture System
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