Long Non-coding RNA as Mediators of Metabolic Disease
长非编码 RNA 作为代谢疾病的介质
基本信息
- 批准号:10083222
- 负责人:
- 金额:$ 20.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-02-01 至 2021-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdipocytesAdipose tissueAnimalsBariatricsBioinformaticsBiologicalBlood CirculationBlood PressureBody Weight decreasedBody mass indexBrown FatCardiometabolic DiseaseCardiovascular DiseasesCell Culture TechniquesCell RespirationCodeCohort StudiesCollaborationsCollectionCommunitiesDataDiabetes MellitusDiagnosticEnergy MetabolismFatty acid glycerol estersFramingham Heart StudyFundingFutureGene ExpressionGene TargetingGenesGenetic TranscriptionHeart failureHomeostasisHumanIndividualInstitutionInsulin ResistanceInterventionInvestigationLinkLipidsMeasurementMeasuresMediatingMediator of activation proteinMessenger RNAMetabolicMetabolic DiseasesMetabolic syndromeMetabolismMethodsMitochondriaModelingMolecularMolecular TargetNational Heart, Lung, and Blood InstituteNorepinephrineNucleotidesObesityOutcomePathogenesisPathway interactionsPhysiologyPlasmaPopulationPopulations at RiskProteinsRNARNA analysisRegulationResearchResolutionResource SharingResourcesRiskRoleSamplingSupraclavicularTherapeuticThermogenesisTimeTissue BanksTissuesTranscriptional RegulationTranslationsUnited States National Institutes of HealthUntranslated RNAValidationVentricular RemodelingVisceral fatbariatric surgerybasebiological systemscardiometabolismcardiovascular healthcardiovascular risk factorclinical centercoronary artery calcificationcost efficientdifferential expressiondisease phenotypeepigenetic regulationextracellularhuman tissuein silicoin vivoinnovationinsightlipid biosynthesismRNA Expressionmannovelobesity treatmentpopulation basedprimary outcomeprogramsprospectivepublic health relevancesecondary outcometargeted biomarkertranscriptome sequencing
项目摘要
Obesity, diabetes, and accompanying lipid and blood pressure dysregulation—collectively termed
“cardiometabolic disease” (CMD)—is a major contributor to cardiovascular disease. Despite long-standing data
implicating small non-coding RNAs in CMD, less is known in regards to long non-coding RNAs (lncRNAs).
Animal studies have recently suggested a role for lncRNAs in lipid homeostasis, fat thermogenesis and
myocardial remodeling, each critical to CMD. While animal studies may heighten a suspicion for lncRNAs in
CMD, studies in human tissue are imperative to establish their role. Studies focused on lncRNA expression in
tissues central to CMD in humans are crucial to understand novel aspects of the molecular physiology of CMD
and its downstream impact on cardiovascular health. Brown adipose tissue (BAT), central in energy
expenditure regulation and metabolism, is inversely correlated with body-mass index (BMI). Preliminary data
from our group using human adipocytes from BAT and white adipose tissue (WAT) has identified specific
lncRNAs that are differentially expressed and altered in proportion with increasing BMI and diabetes. Currently,
in silico determination of lncRNA-mRNA regulation remains problematic (due to lack of curated resources), and
large-scale validation in accessible tissue (e.g., plasma) from populations at-risk for CMD and downstream
cardiovascular risk is lacking. Therefore, understanding the role of lncRNAs in humans must (1) be performed
in human tissues relevant to CMD; (2) identify coordinate changes between lncRNA and mRNA expression (as
possible targets of lncRNA regulation); (3) include association studies between lncRNAs and CMD phenotypes
to enable future larger mechanistic studies in CMD.
Here, we hypothesize that lncRNAs differentially expressed in BAT vs. WAT or relevant in adipogenesis
will be (1) associated with expression of genes central to CMD pathogenesis and (2) dynamically expressed in
plasma as a function of cardiometabolic perturbations known to impact CMD and cardiovascular disease (e.g.,
bariatric surgery, insulin resistance). To address this central hypothesis, we bring together our preliminary
human adipose tissue RNA-seq data with several very unique resources: (1) ongoing WAT, BAT, and plasma
collection from prospective resources at the NIH Clinical Center and our institution; (2) an NIH-funded study of
individuals pre-/post-bariatric surgery in which we have performed non-coding RNA quantification
(U54HL112311) and have preliminary data establishing large changes in lncRNAs with weight loss; (3)
population-wide data (n=3100) including CMD, mRNA measurements, and available RNA for lncRNA
analyses. This application is based on preliminary data providing candidate lncRNAs that are differentially
expressed in metabolically active fat. It is bolstered by active collaborations and samples previously collected
from NIH/NHLBI sponsored studies, as well as innovative bioinformatics methods to identify possible lncRNA
gene targets. All data will be made publically available and created as a shared resource.
肥胖,糖尿病,以及伴随的血脂和血压失调——统称为
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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JANE E Freedman其他文献
JANE E Freedman的其他文献
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{{ truncateString('JANE E Freedman', 18)}}的其他基金
Circulating Proteomics to Phenotype the Development and Reversal of Myocardial Remodeling in Aortic Stenosis
循环蛋白质组学对主动脉瓣狭窄心肌重塑的发展和逆转进行表型分析
- 批准号:
10844786 - 财政年份:2023
- 资助金额:
$ 20.17万 - 项目类别:
Circulating Proteomics to Phenotype the Development and Reversal of Myocardial Remodeling in Aortic Stenosis
循环蛋白质组学对主动脉瓣狭窄心肌重塑的发展和逆转进行表型分析
- 批准号:
10658707 - 财政年份:2023
- 资助金额:
$ 20.17万 - 项目类别:
Long Non-coding RNA as Mediators of Metabolic Disease
长非编码 RNA 作为代谢疾病的介质
- 批准号:
10338074 - 财政年份:2021
- 资助金额:
$ 20.17万 - 项目类别:
Long Non-coding RNA as Mediators of Metabolic Disease
长非编码 RNA 作为代谢疾病的介质
- 批准号:
10496586 - 财政年份:2021
- 资助金额:
$ 20.17万 - 项目类别:
The Effect of Behavioral Weight Loss on Circulating Extracellular RNA
行为减肥对循环细胞外 RNA 的影响
- 批准号:
10041786 - 财政年份:2020
- 资助金额:
$ 20.17万 - 项目类别:
Racial and Ethnic Diversity in Human Extracellular RNA
人类细胞外 RNA 的种族和民族多样性
- 批准号:
8775017 - 财政年份:2014
- 资助金额:
$ 20.17万 - 项目类别:
Extracellular RNAs: Biomarkers for Cardiovascular Risk and Disease
细胞外 RNA:心血管风险和疾病的生物标志物
- 批准号:
8711589 - 财政年份:2013
- 资助金额:
$ 20.17万 - 项目类别:
Extracellular RNAs: Biomarkers for Cardiovascular Risk and Disease
细胞外 RNA:心血管风险和疾病的生物标志物
- 批准号:
9325089 - 财政年份:2013
- 资助金额:
$ 20.17万 - 项目类别:
Extracellular RNAs: Biomarkers for Cardiovascular Risk and Disease
细胞外 RNA:心血管风险和疾病的生物标志物
- 批准号:
9319351 - 财政年份:2013
- 资助金额:
$ 20.17万 - 项目类别:
Extracellular RNAs: Biomarkers for Cardiovascular Risk and Disease
细胞外 RNA:心血管风险和疾病的生物标志物
- 批准号:
8962180 - 财政年份:2013
- 资助金额:
$ 20.17万 - 项目类别:
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