Regulation of Lipolysis by Oxytocin

催产素对脂肪分解的调节

基本信息

项目摘要

ABSTRACT Adipose tissue lipolysis is a critical process that provides nutritional substrate to other organs during periods of fasting. Lipolysis also contributes to the metabolic pathology associated with obesity, as lipid species from adipose tissue promote hepatic glucose production and are also an important contributor to the excess fat seen in nonalcoholic fatty liver disease. Despite the importance of lipolysis in mammalian physiology and pathophysiology, there is still much to be learned about how it is regulated and what its consequences are. There have been reports over the years that the neuropeptide oxytocin (Oxt) is an inducer of lipolysis. Our preliminary data corroborates this, but goes much further in several important areas. First, we show that Oxt signaling is not only required for normal lipolysis in the setting of fasting and cold exposure, but is also needed for b-adrenergic agonists to exert their well-known pro-lipolytic effects. We also identify the relevant source of Oxt as a subpopulation of TH+ sympathetic neurons innervating white adipose depots. In this proposal we intend to fully characterize the intracellular signaling pathways by which Oxt promotes lipolysis. In addition, we will determine the local mechanism by which Oxt levels are controlled through degradation. Finally, we will follow up on preliminary data suggesting that maternal Oxt signaling in fat is required to ensure milk of proper nutritional content during lactation. Taken together, these studies will greatly advance our understanding of lipolysis. Furthermore, Oxt is being pursued as a pharmacological therapy for a variety of conditions, including anxiety and neurodegenerative disorders, and this work will provide important information about potential metabolic side effects.
摘要 脂肪分解是向其他器官提供营养基质的关键过程 在禁食期间。脂解还有助于与以下相关的代谢病理学: 肥胖症,因为来自脂肪组织的脂质种类促进肝葡萄糖产生,并且也是一种 非酒精性脂肪肝中脂肪过多的重要原因。尽管 脂解作用在哺乳动物生理学和病理生理学中重要性,仍有许多工作要做 了解了它是如何被监管的,以及它的后果是什么。有报道称 神经肽催产素(Oxt)是脂解的诱导剂。我们的初步数据 它证实了这一点,但在几个重要领域更进一步。首先,我们表明,Oxt 信号传导不仅是在禁食和冷暴露的情况下正常脂解所必需的, β-肾上腺素能激动剂也需要β-肾上腺素来发挥其公知的促脂解作用。我们也 确定Oxt的相关来源为TH+交感神经元的亚群, 白色脂肪沉积。在这个建议中,我们打算充分表征细胞内信号传导 Oxt促进脂解的途径。此外,我们会根据以下方法, 其中Oxt水平通过降解来控制。最后,我们会跟进初步数据 这表明母体脂肪中的Oxt信号传导是确保乳汁具有适当营养含量所必需的 在哺乳期。总之,这些研究将大大推进我们对脂肪分解的理解。 此外,Oxt正被用作各种疾病的药理学治疗, 包括焦虑和神经退行性疾病,这项工作将提供重要的 关于潜在代谢副作用的信息。

项目成果

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Brigid Ellen Gregg其他文献

Brigid Ellen Gregg的其他文献

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{{ truncateString('Brigid Ellen Gregg', 18)}}的其他基金

The GROWTH Study, Glycemia Range and Offspring Weight and adiposity in response To Human milk
生长研究、血糖范围以及后代体重和肥胖对母乳的反应
  • 批准号:
    10595445
  • 财政年份:
    2023
  • 资助金额:
    $ 57.03万
  • 项目类别:
Programming of beta-cells and Glucose Homeostasis by Maternal Metformin Exposure
母体二甲双胍暴露对 β 细胞和血糖稳态的编程
  • 批准号:
    10426639
  • 财政年份:
    2015
  • 资助金额:
    $ 57.03万
  • 项目类别:
Programming of beta-cells and Glucose Homeostasis by Maternal Metformin Exposure
母体二甲双胍暴露对 β 细胞和血糖稳态的编程
  • 批准号:
    9324994
  • 财政年份:
    2015
  • 资助金额:
    $ 57.03万
  • 项目类别:
Programming of beta-cells and Glucose Homeostasis by Maternal Metformin Exposure
母体二甲双胍暴露对 β 细胞和血糖稳态的编程
  • 批准号:
    9459526
  • 财政年份:
    2015
  • 资助金额:
    $ 57.03万
  • 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:
    321208980
  • 财政年份:
    2016
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    $ 57.03万
  • 项目类别:
    Research Grants
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:
    8827438
  • 财政年份:
    2014
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Induction of brown-like adipocytes in white adipose tissue by food-derived factors
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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    $ 57.03万
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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.
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。
  • 批准号:
    257256526
  • 财政年份:
    2014
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    $ 57.03万
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    Research Fellowships
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:
    8828181
  • 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:
    8520690
  • 财政年份:
    2013
  • 资助金额:
    $ 57.03万
  • 项目类别:
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
  • 财政年份:
    2013
  • 资助金额:
    $ 57.03万
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Effect of exercise training on formation of brite adipocytes within white adipose tissue
运动训练对白色脂肪组织内脂肪细胞形成的影响
  • 批准号:
    23700778
  • 财政年份:
    2011
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    $ 57.03万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Investigation for the mechanisms of the emergence of brown adipocytes in white adipose tissue
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
  • 财政年份:
    2009
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    $ 57.03万
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    Grant-in-Aid for Young Scientists (B)
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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