Testing the Adipose Expandability Hypothesis In Vivo During Overfeeding

过量喂养期间体内脂肪膨胀性假说的检验

基本信息

  • 批准号:
    10321614
  • 负责人:
  • 金额:
    $ 62.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-01-15 至 2025-12-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Adipose expansion is necessary to accommodate chronic excess caloric intake and characterized by an increase in adipocyte size (hypertrophy) and number (hyperplasia; adipogenesis). Though obesity is related to AT lipid handling and storage capacity, the mechanisms underlying the link between obesity and the metabolic syndrome (MetS) are poorly understood. The AT expandability hypothesis postulates that the capacity for subcutaneous (subQ) adipose expansion is a significant determinant of metabolic health, as impaired adipogenesis (limited hyperplasia) may lead to ectopic lipid deposition in non-adipose organs, contributing to the development of obesity-associated diseases. Some in vitro studies report a higher population of small fat cells (i.e. hyperplasia) in individuals with MetS and type 2 diabetes. Data from two human overfeeding studies (one from our group) demonstrate that a smaller adipocyte size resulted in a greater impairment of insulin sensitivity with weight gain. We are the only group to assess in vivo adipogenesis in subQ AT via the incorporation of deuterium (2H) into adipose cells of obese women and show that higher adipocyte formation was associated with facets of impaired metabolic health. Our findings and others are contrary to the AT expandability hypothesis and provide evidence that higher (not lower) adipogenesis (i.e. hyperplasia) is associated with obesity-related disorders. Using a randomized controlled trial (RCT), we will examine the effects of a 9-week intervention on mechanisms of AT expandability. Overweight men and women will be randomized to 30% overfeeding (OF) or a weight stable Control (CTL) group. The objectives of the proposal are to test in vivo adipogenesis, using a validated 2H-labeling approach, and other mechanisms of subQ AT expansion in response to weight gain, and to assess the relationship of adipose expansion with changes in metabolic outcomes. The primary hypothesis is that higher adipogenesis in response to OF will be accompanied by increased visceral adiposity and ectopic lipid, reduced insulin sensitivity, and pathological AT remodeling in individuals with impaired subQ AT expansion. Therefore, despite hyperplasia in weight gainers, a limited storage capacity of adipocytes may facilitate impaired health outcomes. This is the first RCT to test the validity of the `AT expandability hypothesis'. Findings will provide new knowledge on the influence of adipose characteristics on the metabolic responses to dynamic changes in weight in humans.
项目总结/摘要 脂肪扩张对于适应慢性过量热量摄入是必要的,其特征是 脂肪细胞大小(肥大)和数量(增生;脂肪形成)增加。虽然肥胖与 脂肪处理和储存能力,肥胖和代谢之间联系的潜在机制, 综合征(MetS)了解甚少。AT可扩展性假设假定, 皮下(subQ)脂肪扩张是代谢健康的重要决定因素, 脂肪生成(有限增生)可能导致非脂肪器官中的异位脂质沉积,导致 肥胖相关疾病的发展。一些体外研究报告说, (i.e.增生)。来自两项人类过度喂养研究的数据(一项 来自我们小组的研究)表明,较小的脂肪细胞大小导致胰岛素敏感性的更大损害 体重增加。我们是唯一一个通过掺入以下物质来评估subQ AT体内脂肪形成的小组: 氘(2 H)进入肥胖妇女的脂肪细胞,并表明更高的脂肪细胞形成与 代谢健康受损的各个方面。我们的研究结果和其他研究结果与AT可扩展性假设相反, 提供证据表明,较高(而不是较低)的脂肪形成(即增生)与肥胖相关 紊乱使用随机对照试验(RCT),我们将检查9周干预对 AT可扩展性机制。超重的男性和女性将被随机分配至30%的过度喂养(OF)或 体重稳定对照(CTL)组。该提案的目的是测试体内脂肪形成,使用 经验证的2 H-标记方法,以及响应体重增加的subQ AT扩张的其他机制,以及 评估脂肪膨胀与代谢结果变化的关系。主要假设为 高脂肪生成反应OF将伴随增加内脏脂肪和异位 血脂、胰岛素敏感性降低和病理性AT重构。 因此,尽管在体重增加者中存在增生,但脂肪细胞的有限储存能力可能促进受损的 健康成果。这是第一个随机对照试验,以测试的有效性“AT扩展性假设”。调查结果将提供 关于脂肪特性对代谢反应的影响的新知识, 人类的体重。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Ursula White其他文献

Ursula White的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Ursula White', 18)}}的其他基金

Testing the Adipose Expandability Hypothesis In Vivo During Overfeeding
过量喂养期间体内脂肪膨胀性假说的检验
  • 批准号:
    9913339
  • 财政年份:
    2020
  • 资助金额:
    $ 62.08万
  • 项目类别:
The Regulation and Metabolic Effects of gp130 Cytokines in Human White Adipose Ti
人白脂肪Ti中gp130细胞因子的调节和代谢作用
  • 批准号:
    8768073
  • 财政年份:
    2014
  • 资助金额:
    $ 62.08万
  • 项目类别:

相似国自然基金

相似海外基金

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
  • 资助金额:
    $ 62.08万
  • 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
  • 资助金额:
    $ 62.08万
  • 项目类别:
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
  • 批准号:
    26450168
  • 财政年份:
    2014
  • 资助金额:
    $ 62.08万
  • 项目类别:
    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
  • 资助金额:
    $ 62.08万
  • 项目类别:
    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
  • 资助金额:
    $ 62.08万
  • 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:
    8520690
  • 财政年份:
    2013
  • 资助金额:
    $ 62.08万
  • 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:
    $ 62.08万
  • 项目类别:
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
  • 资助金额:
    $ 62.08万
  • 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
  • 批准号:
    21780261
  • 财政年份:
    2009
  • 资助金额:
    $ 62.08万
  • 项目类别:
    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
  • 批准号:
    7610781
  • 财政年份:
    2007
  • 资助金额:
    $ 62.08万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了