MiR-33 and Aging: Implications for Metabolic Syndrome

MiR-33 和衰老:对代谢综合征的影响

基本信息

  • 批准号:
    8397633
  • 负责人:
  • 金额:
    $ 4.22万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-07-02 至 2015-07-01
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The metabolism of cholesterol and fatty acids, essential components of many biochemical pathways, is tightly regulated at the cellular level. Insufficient or excess levels can be detrimental to cells and are associated with aging-related diseases such as atherosclerosis, type 2 diabetes, and metabolic syndrome. Many regulatory pathways exist to ensure that cholesterol and fatty acid levels are balanced. In particular, recent findings have revealed a crucial role for small non-coding RNAs (miRNAs) in the post-transcriptional control of cholesterol and lipoprotein-related genes. Of note is microRNA-33 (miR-33), an intronic miRNA located within the sterol regulatory element-binding protein (SREBP) gene, one of the master regulators of cholesterol and fatty acid metabolism. miR-33 regulates cholesterol efflux and high density lipoprotein (HDL) formation in concert with the SREBP host genes, suggesting an important role for miRNAs in the regulation of cholesterol metabolism. miR-33 has also recently been to shown to regulate fatty acid metabolism and insulin signaling. miR-33 binds and represses key enzymes involved in the regulation of fatty acid oxidation, including carnitine O-octaniltransferase (CROT), carnitine palmitoyltransferase 1A (CPT1a), and hydroxyacyl-CoA-dehydrogenase (HADHB). In addition, miR-33 also targets the insulin receptor substrate 2 (IRS2), an essential component of the insulin- signaling pathway. Overexpression of miR-33 reduces both fatty acid oxidation and insulin signaling in hepatic cell lines, whereas endogenous inhibition of miR-33 increases these two metabolic pathways. In this proposal, we hypothesize that miR-33 regulates pathways controlling three of the risk factors of metabolic syndrome, including levels of HDL, triglycerides, and insulin signaling and that miR-33 may be useful as a therapeutic target to treat this growing health concern. PUBLIC HEALTH RELEVANCE: The research proposed has significant implications in the field of lipid biology and cardiology- both key issues in aging that impact mortality and quality of life This work is intended to characterize a novel regulator of cholesterol, lipid, and glucose metabolism in liver cells and in mice fed a chow and high-fat diet. This work will also address how this regulator may impact risk factors that increase the chance of developing heart disease, stroke, and type 2 diabetes- important diseases and consequences of aging.
描述(由申请人提供):胆固醇和脂肪酸的代谢是许多生化途径的重要组成部分,在细胞水平受到严格调控。不足或过量的水平可能对细胞有害,并与衰老相关的疾病,如动脉粥样硬化,2型糖尿病和代谢综合征有关。存在许多调节途径以确保胆固醇和脂肪酸水平平衡。特别是最近 研究结果揭示了小的非编码RNA(miRNAs)在胆固醇和脂蛋白相关基因的转录后控制中的关键作用。值得注意的是microRNA-33(miR-33),一种位于固醇调节元件结合蛋白(SREBP)基因内的内含子miRNA,是胆固醇和脂肪酸代谢的主要调节因子之一。miR-33与SREBP宿主基因一起调节胆固醇流出和高密度脂蛋白(HDL)形成,表明miRNA在胆固醇代谢调节中的重要作用。最近还显示miR-33调节脂肪酸代谢和胰岛素信号传导。miR-33结合并抑制参与调节脂肪酸氧化的关键酶,包括肉毒碱O-辛醇转移酶(CROT)、肉毒碱棕榈酰转移酶1A(CPT 1a)和羟酰辅酶A脱氢酶(HADHB)。此外,miR-33还靶向胰岛素受体底物2(IRS 2),这是胰岛素信号传导途径的重要组成部分。在肝细胞系中,miR-33的过表达减少脂肪酸氧化和胰岛素信号传导,而miR-33的内源性抑制增加这两种代谢途径。在这个提议中,我们假设miR-33调节控制代谢综合征的三个风险因素的途径,包括HDL,甘油三酯和胰岛素信号传导的水平,并且miR-33可能用作治疗这种日益增长的健康问题的治疗靶点。 公共卫生相关性:这项研究在脂质生物学和心脏病学领域具有重要意义-这两个问题都是影响死亡率和生活质量的衰老问题。这项工作旨在表征肝细胞和喂食食物和高脂肪饮食的小鼠中胆固醇,脂质和葡萄糖代谢的新型调节剂。这项工作还将解决这种调节剂如何影响风险因素,增加患心脏病,中风和2型糖尿病的机会-重要的疾病和衰老的后果。

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(1)

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Leigh Goedeke其他文献

Leigh Goedeke的其他文献

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{{ truncateString('Leigh Goedeke', 18)}}的其他基金

Cellular and molecular mechanisms of diabetic atherosclerosis
糖尿病动脉粥样硬化的细胞和分子机制
  • 批准号:
    10662558
  • 财政年份:
    2022
  • 资助金额:
    $ 4.22万
  • 项目类别:
Cellular and molecular mechanisms of diabetic atherosclerosis
糖尿病动脉粥样硬化的细胞和分子机制
  • 批准号:
    10556834
  • 财政年份:
    2022
  • 资助金额:
    $ 4.22万
  • 项目类别:
Effect of Liver-Specific Acetyl-CoA Carboxylase Inhibition on Hepatic Steatosis and Insulin Resistance
肝脏特异性乙酰辅酶A羧化酶抑制对肝脏脂肪变性和胰岛素抵抗的影响
  • 批准号:
    9467827
  • 财政年份:
    2017
  • 资助金额:
    $ 4.22万
  • 项目类别:
MiR-33 and Aging: Implications for Metabolic Syndrome
MiR-33 和衰老:对代谢综合征的影响
  • 批准号:
    8536576
  • 财政年份:
    2012
  • 资助金额:
    $ 4.22万
  • 项目类别:

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