Methionine Aminopeptidase 2 Regulates Lipid Metabolism in Peripheral Tissues

蛋氨酸氨基肽酶 2 调节外周组织中的脂质代谢

基本信息

  • 批准号:
    10388782
  • 负责人:
  • 金额:
    $ 3.52万
  • 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:
    2019-12-01 至 2022-05-31
  • 项目状态:
    已结题

项目摘要

Project Summary Obesity is the result of a chronic, relapsing progressive disease process that has become a global pandemic. Reductions in weight as small as 5-10% drastically help reduce the comorbidities of obesity, however weight loss is extremely difficult to maintain. Anti-obesity drugs are promising interventions to help overcome the challenge of maintaining weight loss, yet most have been withdrawn due to serious side effects. For this reason, further research is needed on strategies for producing sustained weight loss. One drug class currently being tested in clinical trails, methionine aminopeptidase 2 (MetAP2) inhibitors, rapidly reduce body weight, increase glycemic control, and reduce serum lipids. Remarkably, clinical trials with MetAP2i are ongoing despite the fact we know little about how MetAP2 mediates anti-obesogenic effects. In vitro studies have shown that MetAP2 is a multifunctional protein that removes the N-terminal methionine residue from newly translated proteins, but can also directly impact major cell signaling pathways. In the past, it has been challenging to study the effects of MetAP2 expression in vivo, because the developmental models of MetAP2 elimination are embryonically lethal. To overcome this problem, we have generated mouse models that overexpress or knockdown MetAP2 in an inducible, tissue-specific manner. These mouse models will allow us to examine the systemic effects and molecular mechanisms of MetAP2 expression in two major peripheral organs that regulate glucose and lipid metabolism during obesity: liver and adipose tissue. Only after understanding the mechanisms that underlie the cellular effects of MetAP2, will we begin to understand how MetAP2 or MetAP2 inhibitors take part in the complex regulation of whole-body energy balance. Specifically, in Aim 1 we will determine whether MetAP2 expression in adipocytes and hepatocytes regulate body weight, energy expenditure, glucose tolerance, and serum lipid levels. The goal of Aim 2 is to examine whether the three known MetAP2 mechanisms discovered in vitro are found to be relevant to liver and adipose tissue lipid metabolism in vivo.
项目总结

项目成果

期刊论文数量(1)
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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Christy M Gliniak其他文献

Christy M Gliniak的其他文献

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{{ truncateString('Christy M Gliniak', 18)}}的其他基金

Interaction of Mesenteric Adipose Tissue Physiology, Expansion, and Inflammation with Inflammatory Bowel Disease
肠系膜脂肪组织生理学、扩张和炎症与炎症性肠病的相互作用
  • 批准号:
    10590505
  • 财政年份:
    2023
  • 资助金额:
    $ 3.52万
  • 项目类别:
Methionine Aminopeptidase 2 Regulates Lipid Metabolism in Peripheral Tissues
蛋氨酸氨基肽酶 2 调节外周组织中的脂质代谢
  • 批准号:
    9906745
  • 财政年份:
    2019
  • 资助金额:
    $ 3.52万
  • 项目类别:

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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
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    26450168
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    Grant-in-Aid for Scientific Research (C)
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WAT-on-a-chip - 开发微流体、微生理体外脂肪组织模型,用于基于 hiPSC 衍生脂肪细胞的高通量药物筛选。
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增强白色脂肪组织中的能量消耗脂肪细胞
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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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    $ 3.52万
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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
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    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
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    2007
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