Estrogen-Related Receptor Pathways in Skeletal Muscle

骨骼肌中雌激素相关受体途径

基本信息

  • 批准号:
    9319399
  • 负责人:
  • 金额:
    $ 36.45万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-08-01 至 2020-07-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Skeletal muscle plays key roles in glucose and lipid homeostasis, and contributes to whole body energy expenditure. Poor physical fitness and inactivity are risk factors for developing type 2 diabetes, a disease reaching epidemic proportions. Conversely, physical activity is effective in improving metabolic health, by enhancing insulin sensitivity and improving lipid parameters. Interestingly, both the capacity for exercise, and the metabolic benefits and responses to exercise, vary greatly among individuals and are decreased in some disease states. Thus, elucidating the mechanisms that determine muscle function and fitness (and thereby enable exercise), and mediate exercise-induced skeletal muscle responses, is important for finding new ways to target muscle and improve metabolic health. The family of estrogen-related receptors (ERR, ERR and ERR) regulates oxidative metabolism and other pathways important for energy homeostasis. As members of the nuclear receptor family, ERRs have pockets that accommodate synthetic ligands and can thus be targeted therapeutically. Our preliminary data show that all three members of the family are expressed in skeletal muscle and activated by exercise signals. We also show that ERRs collectively determine the expression of genes important for metabolic and contractile properties of skeletal muscle. In the proposed work, we will use mice lacking ERRs specifically in skeletal muscle, to define the cellular and physiologic functions of ERR, ERR and ERR in skeletal muscle, at the basal state and in adaptive responses to endurance exercise. We will also use gain- and loss-of- function approaches in vivo to delineate the physiological function and mechanism of action of Perm1, a novel ERR downstream effector that we recently identified as regulating skeletal muscle oxidative capacity. Overall, we expect to provide novel insights into regulatory mechanisms that enable and shape skeletal muscle adaptive responses to endurance exercise, and to inform on pathways relevant to disease states where oxidative metabolism and muscle function are compromised, such as insulin resistance and type 2 diabetes, disease-associated or injury-caused muscle atrophies, and age-related muscle degeneration. Our findings will be important for guiding future efforts to use ERR/ agonists o enhance muscle function and/or benefits from exercise.
 描述(由申请人提供):骨骼肌在葡萄糖和脂质体内平衡中起关键作用,并有助于全身能量消耗。身体素质差和缺乏活动是发展2型糖尿病的危险因素,这种疾病已达到流行病的程度。相反,体力活动通过增强胰岛素敏感性和改善脂质参数,有效改善代谢健康。有趣的是,运动能力以及代谢益处和对运动的反应在个体之间差异很大,并且在某些疾病状态下会降低。因此,阐明决定肌肉功能和健身(从而使运动),并介导运动诱导的骨骼肌反应的机制,对于寻找靶向肌肉和改善代谢健康的新方法很重要。雌激素相关受体家族(ERR β、ERR β和ERR β)调节氧化代谢和其他对能量稳态很重要的途径。作为核受体家族的成员,ERR具有容纳合成配体的口袋,因此可以在治疗上靶向。我们的初步数据显示,该家族的所有三个成员都在骨骼肌中表达,并被运动信号激活。我们还表明,ERRs共同决定了骨骼肌的代谢和收缩特性的重要基因的表达。在拟议的工作中,我们将使用缺乏ERRs的小鼠,特别是在骨骼肌中,以确定在基础状态和耐力运动的适应性反应的骨骼肌中的ERR β,ERR β和ERR β的细胞和生理功能。我们还将在体内使用获得和丧失功能的方法来描述Perm 1的生理功能和作用机制,Perm 1是一种新的ERR下游效应物,我们最近确定为调节骨骼肌氧化能力。总的来说,我们希望提供新的见解,使调节机制,使和形状骨骼肌适应性反应耐力运动,并告知相关的途径,疾病状态的氧化代谢和肌肉功能受到损害,如胰岛素抵抗和2型糖尿病,疾病相关或损伤引起的肌肉萎缩,和年龄相关的肌肉退化。我们的发现对于指导未来使用ERR β/β激动剂来增强肌肉功能和/或从运动中获益的努力将是重要的。

项目成果

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Anastasia Kralli其他文献

Anastasia Kralli的其他文献

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{{ truncateString('Anastasia Kralli', 18)}}的其他基金

Regulators of adipocyte oxidative metabolism
脂肪细胞氧化代谢的调节因子
  • 批准号:
    10632187
  • 财政年份:
    2022
  • 资助金额:
    $ 36.45万
  • 项目类别:
Regulators of adipocyte oxidative metabolism
脂肪细胞氧化代谢的调节因子
  • 批准号:
    10391144
  • 财政年份:
    2021
  • 资助金额:
    $ 36.45万
  • 项目类别:
Regulators of adipocyte oxidative metabolism
脂肪细胞氧化代谢的调节因子
  • 批准号:
    10532240
  • 财政年份:
    2021
  • 资助金额:
    $ 36.45万
  • 项目类别:
Regulators of adipocyte oxidative metabolism
脂肪细胞氧化代谢的调节因子
  • 批准号:
    10673362
  • 财政年份:
    2021
  • 资助金额:
    $ 36.45万
  • 项目类别:
Estrogen-Related Receptor Pathways in Skeletal Muscle
骨骼肌中雌激素相关受体途径
  • 批准号:
    9324242
  • 财政年份:
    2016
  • 资助金额:
    $ 36.45万
  • 项目类别:
Estrogen-Related Receptor Pathways in Skeletal Muscle
骨骼肌中雌激素相关受体途径
  • 批准号:
    9029852
  • 财政年份:
    2015
  • 资助金额:
    $ 36.45万
  • 项目类别:
The Role of Estrogen-Related Receptors in Energy Homeostasis
雌激素相关受体在能量稳态中的作用
  • 批准号:
    8876661
  • 财政年份:
    2012
  • 资助金额:
    $ 36.45万
  • 项目类别:
The Role of Estrogen-Related Receptors in Energy Homeostasis
雌激素相关受体在能量稳态中的作用
  • 批准号:
    8708064
  • 财政年份:
    2012
  • 资助金额:
    $ 36.45万
  • 项目类别:
The Role of Estrogen-Related Receptors in Energy Homeostasis
雌激素相关受体在能量稳态中的作用
  • 批准号:
    8534114
  • 财政年份:
    2012
  • 资助金额:
    $ 36.45万
  • 项目类别:
The Role of Estrogen-Related Receptors in Energy Homeostasis
雌激素相关受体在能量稳态中的作用
  • 批准号:
    8401824
  • 财政年份:
    2012
  • 资助金额:
    $ 36.45万
  • 项目类别:

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