15 BEDREST: Targeting bed rest-induced adipose tissue dysfunction with anti-inflammatory & antioxidant nutrients

15 BEDREST:通过抗炎治疗卧床休息引起的脂肪组织功能障碍

基本信息

  • 批准号:
    BB/N004809/1
  • 负责人:
  • 金额:
    $ 55.75万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2015
  • 资助国家:
    英国
  • 起止时间:
    2015 至 无数据
  • 项目状态:
    已结题

项目摘要

Bed rest is a useful experimental model of physiological deconditioning which is analogous to accelerated ageing in an increasingly sedentary population. As part of the ELIPS programme, the European Space Agency are planning a long-term bed rest study to determine the impact of a nutritional anti-inflammatory and antioxidant countermeasure (including resveratrol, vitamins E and C, lycopene and epigallocatechin). We hypothesise that bed rest will lead to inflammatory and metabolic disturbances in subcutaneous adipose tissue (fat) which mimic many of the changes in this tissue seen with ageing and physical inactivity - and that the planned countermeasures will offset the changes induced by bed rest.Collectively, our understanding of adipose tissue has changed enormously in recent years and adipose tissue is clearly much more than a simple energy store. Adipose tissue is an active player in diverse physiological systems ranging from bone remodelling through to muscle substrate (fuel) utilisation. Adipose tissue communicates with other tissues via the secretion of archetypal 'adipokines' (e.g., adiponectin) but adipose tissue is also responsible for the secretion of many other proteins and mediators which have implications for other distant tissues including muscle and bone. We hypothesise that increased glucose uptake by adipose tissue in response to bed rest will provoke cellular and oxidative stress - causing adipocytes to secrete/express molecules designed in part to initiate an immune response but which then exacerbates adipose dysfunction. We will take adipose tissue biopsies before and after 60-d bed rest in both control and intervention groups (n=8 to 12 in each group). We will determine changes in whole adipose tissue at both gene expression and protein levels. Since we cannot assume that bed rest and the anti-inflammatory and antioxidant countermeasures will elicit equal effects in the heterogeneous cells that comprise adipose tissue, we will separate adipocytes from non-adipocytes (e.g. immune cells) and examine adipocytes and immune cells separately. We will determine adipocyte glucose uptake in basal and insulin-stimulated conditions. We will examine changes in the number of specific immune cells that are resident within adipose (e.g. macrophages) and also whether these cells have a pro- or anti-inflammatory phenotype. We will culture small pieces of adipose tissue to examine changes in adipokine secretion - and whether the pattern and amount of selected adipokines is impacted upon by bed rest. Finally, we will undertake exploratory work to examine whether altered adipokine secretion with bed rest has the potential to impact upon bone and muscle cell models. Virtually all of the above work will be conducted in the UK using frozen samples.Importantly, the planned countermeasures have the potential to positively impact upon adipose tissue function from the earliest mechanistic step (e.g., resveratrol and epigallocatechin decrease adipose tissue glucose uptake) all the way through to downstream consequences related to secondary oxidative stress and inflammation (e.g., all of the ingredients have been shown to target either oxidative stress and/or inflammation in adipose tissue). To date, most of these mechanisms have only been examined in rodent adipose tissue and thus the planned intervention represents an excellent opportunity to verify whether we can translate these exciting findings into humans. Adipose tissue dysfunction has been implicated in the aetiology of ageing, diabetes, and cardiovascular disease - with physical inactivity being a potential common mediator. In this context, this research will (i) characterise bed rest-induced adipose tissue dysfunction, (ii) demonstrate whether these changes have implications for other tissues (i.e. muscle and bone) and (iii) determine whether the anti-inflammatory and antioxidant countermeasures successfully target adipose tissue dysfunction in humans.
卧床休息是一个有用的实验模型的生理失调,这是类似于加速老化,在越来越多的久坐不动的人口。作为ELIPS方案的一部分,欧洲航天局正在计划进行一项长期卧床研究,以确定营养抗炎和抗氧化对策(包括白藜芦醇、维生素E和C、番茄红素和表没食子儿茶素)的影响。我们假设,卧床休息会导致皮下脂肪组织(脂肪)的炎症和代谢紊乱,这与衰老和缺乏体力活动时皮下脂肪组织的许多变化相似,而计划的对策将抵消卧床休息引起的变化。总的来说,近年来我们对脂肪组织的理解发生了巨大变化,脂肪组织显然不仅仅是一个简单的能量储存。脂肪组织在从骨重塑到肌肉基质(燃料)利用的各种生理系统中是一个活跃的参与者。脂肪组织通过分泌原型“脂肪因子”(例如,脂联素),但脂肪组织也负责分泌许多其它蛋白质和介质,这些蛋白质和介质对其它远距离组织(包括肌肉和骨骼)具有影响。我们假设,脂肪组织对卧床休息的葡萄糖摄取增加将引起细胞和氧化应激,导致脂肪细胞分泌/表达分子,部分用于启动免疫应答,但随后加剧脂肪功能障碍。我们将在对照组和干预组(每组n=8至12)卧床休息60天前后进行脂肪组织活检。我们将在基因表达和蛋白质水平上确定整个脂肪组织的变化。由于我们不能假设卧床休息和抗炎和抗氧化剂对抗措施将在构成脂肪组织的异质细胞中引起相同的作用,因此我们将脂肪细胞与非脂肪细胞(例如免疫细胞)分离,并分别检查脂肪细胞和免疫细胞。我们将测定基础和胰岛素刺激条件下脂肪细胞的葡萄糖摄取。我们将检查脂肪内特定免疫细胞(如巨噬细胞)数量的变化,以及这些细胞是否具有促炎或抗炎表型。我们将培养小块脂肪组织,以检查脂肪因子分泌的变化-以及所选脂肪因子的模式和数量是否受到卧床休息的影响。最后,我们将进行探索性的工作,以检查是否改变脂肪因子分泌与卧床休息有可能影响骨和肌肉细胞模型。几乎所有上述工作都将在英国使用冷冻样本进行。重要的是,计划的对策有可能从最早的机械步骤(例如,白藜芦醇和表没食子儿茶素降低脂肪组织葡萄糖摄取)一直到与继发性氧化应激和炎症相关的下游后果(例如,所有的成分都显示出靶向脂肪组织中的氧化应激和/或炎症)。到目前为止,这些机制中的大多数只在啮齿动物脂肪组织中进行了研究,因此计划的干预是一个很好的机会来验证我们是否可以将这些令人兴奋的发现转化为人类。脂肪组织功能障碍与衰老、糖尿病和心血管疾病的病因有关,而缺乏身体活动是一种潜在的常见媒介。在这种情况下,本研究将(i)卧床休息引起的脂肪组织功能障碍,(ii)证明这些变化是否对其他组织(即肌肉和骨骼)有影响,(iii)确定抗炎和抗氧化措施是否成功靶向人体脂肪组织功能障碍。

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Impact of Long-term Physical Inactivity on Adipose Tissue Immunometabolism.
长期身体不活跃对脂肪组织免疫代谢的影响。
The impact of physical inactivity on glucose homeostasis when diet is adjusted to maintain energy balance in healthy, young males
调整饮食以维持健康年轻男性的能量平衡时,缺乏身体活动对葡萄糖稳态的影响
  • DOI:
    10.1016/j.clnu.2023.02.006
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    6.3
  • 作者:
    Trim W
  • 通讯作者:
    Trim W
Parallels in Immunometabolic Adipose Tissue Dysfunction with Ageing and Obesity.
  • DOI:
    10.3389/fimmu.2018.00169
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    7.3
  • 作者:
    Trim W;Turner JE;Thompson D
  • 通讯作者:
    Thompson D
Encyclopedia of Behavioral Medicine
行为医学百科全书
  • DOI:
    10.1007/978-1-4614-6439-6_101903-1
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Trim W
  • 通讯作者:
    Trim W
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Dylan Thompson其他文献

Cardiometabolic Markers are Associated With Body Composition but not Physical Activity in Persons With Paraplegia
  • DOI:
    10.1016/j.apmr.2017.08.059
  • 发表时间:
    2017-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Tom Nightingale;Jean-Philippe Walhin;Dylan Thompson;James Bilzon
  • 通讯作者:
    James Bilzon
Hydration status affects thirst and salt preference but not energy intake or postprandial ghrelin in healthy adults: A randomised control trial
水合状态影响健康成年人的口渴和盐偏好,但不影响能量摄入或餐后生长素释放肽:一项随机对照试验
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    H. Carroll;Iain Templeman;Yung;R. Edinburgh;K. Elaine;Burch;Jake T. Jewitt;Georgie Povey;Timothy D. Robinson;William L. Dooley;Charlotte Buckley;Peter J. Rogers;W. Gallo;Olle Melander;Dylan Thompson;Lewis;J. James;Laura Johnson;J. Betts
  • 通讯作者:
    J. Betts
Upper-Body Exercise Improves Indices of Physical and Psychological Functioning in Persons With Spinal Cord Injury
  • DOI:
    10.1016/j.apmr.2017.08.055
  • 发表时间:
    2017-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    James Bilzon;Peter Rouse;Jean-Philippe Walhin;Dylan Thompson;Tom Nightingale
  • 通讯作者:
    Tom Nightingale
The Understanding and Interpretation of Innovative Technology-Enabled Multidimensional Physical Activity Feedback in Patients at Risk of Future Chronic Disease
对未来慢性病风险患者的创新技术支持的多维身体活动反馈的理解和解释
  • DOI:
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    M. Western;O. Peacock;A. Stathi;Dylan Thompson
  • 通讯作者:
    Dylan Thompson
Current and emerging 3D visualization technologies in radiology.
放射学中当前和新兴的 3D 可视化技术。
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    2.3
  • 作者:
    Zachary Abramson;Dylan Thompson;Chris Goode;Cara E Morin;Sarah Daniels;A. Choudhri;Andrew M Davidoff
  • 通讯作者:
    Andrew M Davidoff

Dylan Thompson的其他文献

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{{ truncateString('Dylan Thompson', 18)}}的其他基金

ESTABLISHING THE ROLE OF ADIPOSE TISSUE INFLAMMATION IN THE REGULATION OF MUSCLE MASS IN OLDER PEOPLE
确定脂肪组织炎症在老年人肌肉质量调节中的作用
  • 批准号:
    BB/Y006542/1
  • 财政年份:
    2024
  • 资助金额:
    $ 55.75万
  • 项目类别:
    Research Grant
Mobilising vitamin D sequestered in adipose tissue in humans
动员人体脂肪组织中的维生素 D
  • 批准号:
    BB/R018928/1
  • 财政年份:
    2018
  • 资助金额:
    $ 55.75万
  • 项目类别:
    Research Grant
Personalised social marketing of multi-dimensional physical activity profiles in at risk men & women
对高危男性进行多维体育活动概况的个性化社会营销
  • 批准号:
    MR/J00040X/1
  • 财政年份:
    2012
  • 资助金额:
    $ 55.75万
  • 项目类别:
    Research Grant
BBSRC Industrial CASE Partnership Grant
BBSRC 工业案例合作伙伴资助
  • 批准号:
    BB/I532110/1
  • 财政年份:
    2010
  • 资助金额:
    $ 55.75万
  • 项目类别:
    Training Grant

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Dietary nitrate: therapeutic potential and mechanism-of-action in the prevention of compromised health during short-term bedrest in humans
膳食硝酸盐:预防人类短期卧床期间健康受损的治疗潜力和作用机制
  • 批准号:
    478546
  • 财政年份:
    2023
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    $ 55.75万
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Putting the Brain to Bed: The Importance of Preserving Muscle Health and Cardiovascular Fitness for Cognitive Health during Bedrest
让大脑上床睡觉:卧床休息期间保持肌肉健康和心血管健康对认知健康的重要性
  • 批准号:
    485897
  • 财政年份:
    2022
  • 资助金额:
    $ 55.75万
  • 项目类别:
    Studentship Programs
The Effect of Short-term Bedrest on Mitochondrial Function and Skeletal Muscle Mass in Females and Males
短期卧床对女性和男性线粒体功能和骨骼肌质量的影响
  • 批准号:
    570061-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 55.75万
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    Postgraduate Scholarships - Doctoral
Effectiveness of artificial gravity to maintain muscle strength and neuromuscular interaction during 60 days of bedrest
人工重力在 60 天卧床休息期间维持肌肉力量和神经肌肉相互作用的有效性
  • 批准号:
    409520867
  • 财政年份:
    2018
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    $ 55.75万
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BEDREST Determination of the time-course of the development of insulin resistance, and associated molecular and muscular adaptations during prolonged
BEDREST 确定胰岛素抵抗发展的时间过程,以及长时间期间相关的分子和肌肉适应
  • 批准号:
    BB/P005004/1
  • 财政年份:
    2017
  • 资助金额:
    $ 55.75万
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    Research Grant
15 BEDREST Effects of bed rest on the circadian organisation of the human transcriptome as a model for temporal dysregulation in an ageing population
15 BEDREST 卧床休息对人类转录组昼夜节律组织的影响作为老龄化人群时间失调的模型
  • 批准号:
    BB/N004981/1
  • 财政年份:
    2015
  • 资助金额:
    $ 55.75万
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The effects of 21-days of combined hypoxia and bedrest on cerebral blood flow regulation
联合缺氧卧床21天对脑血流调节的影响
  • 批准号:
    434695-2012
  • 财政年份:
    2012
  • 资助金额:
    $ 55.75万
  • 项目类别:
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STRESS RESPONSE TO NON-WEIGHT BEARING BEDREST
对非负重卧床的应激反应
  • 批准号:
    7608208
  • 财政年份:
    2007
  • 资助金额:
    $ 55.75万
  • 项目类别:
Neural control of circulation in aging and bedrest
衰老和卧床时循环的神经控制
  • 批准号:
    319446-2005
  • 财政年份:
    2007
  • 资助金额:
    $ 55.75万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
BEDREST AND AGING: PROJECT 2 EXERCISE AND MUSCLE
卧床休息和衰老:项目 2 锻炼和肌肉
  • 批准号:
    7377685
  • 财政年份:
    2006
  • 资助金额:
    $ 55.75万
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