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

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

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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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Recruitment of brown adipocytes in visceral white adipose tissue by fibroblast growth factor 8b
成纤维细胞生长因子 8b 将棕色脂肪细胞募集到内脏白色脂肪组织中
  • 批准号:
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    2016
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Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
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    8827438
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食物源性因子在白色脂肪组织中诱导棕色样脂肪细胞
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    26450168
  • 财政年份:
    2014
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    $ 20.17万
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    Grant-in-Aid for Scientific Research (C)
WAT-on-a-chip - Development of a micofluidic, microphysiologic in vitro adipose tissue model for high-throughput drug screening based on hiPSC-derived adipocytes.
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  • 批准号:
    257256526
  • 财政年份:
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Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
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    8520690
  • 财政年份:
    2013
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Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8629741
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    2013
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运动训练对白色脂肪组织内脂肪细胞形成的影响
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    23700778
  • 财政年份:
    2011
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    Grant-in-Aid for Young Scientists (B)
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白色脂肪组织中棕色脂肪细胞出现机制的研究
  • 批准号:
    21780261
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    2009
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LOUISIANA COBRE: P1: INDUCE THERMOGENIC BROWN ADIPOCYTES IN WHITE ADIPOSE TISSUE
路易斯安那 COBRE:P1:在白色脂肪组织中诱导产热棕色脂肪细胞
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    7610781
  • 财政年份:
    2007
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