Physiological changes underlying the weight loss plateau in humans

人类减肥平台期的生理变化

基本信息

  • 批准号:
    10734323
  • 负责人:
  • 金额:
    $ 78.91万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-08-01 至 2027-07-31
  • 项目状态:
    未结题

项目摘要

Behavioral strategies for obesity treatment reliably result in weight loss and health benefits. However, weight loss typically plateaus at ~7–10% of total body weight (a plateau phase) after which weight regain is common, limiting the ability of most intervention strategies to modify obesity-related disease risk in a sustained manner. Overcoming these limitations requires advancing understanding of metabolic, appetitive, and neurological factors that counteract—and eventually halt—weight loss. Existing literature shows that weight loss evokes appetitive adaptations that include increased hunger and decreased satiety. The investigative team’s preliminary data add evidence that an impaired satiety response in brain regions controlling reward and motivation follows weight loss. Documented metabolic responses to weight loss include declines in total body and resting energy expenditure as well as increased metabolic efficiency in muscle and adipose tissue. We now present preliminary data using novel measures of mitochondrial metabolism indicating that a weight loss plateau is characterized by reductions in mitochondrial metabolic capacity in peripheral blood mononuclear cells. The proposed research aims to 1) test if an involuntary weight loss plateau is distinguished from other phases of weight loss by alterations in cellular bioenergetics across multiple tissue types including circulating blood cells, muscle, and adipose tissue; 2) test for neurophysiologic changes consistent with reduced satiety at an involuntary weight loss plateau and assess their relation to changes in metabolism; and 3) investigate predictors of a weight loss plateau using data collected at baseline and in real time during behavioral weight loss. To address these three Specific Aims, the multidisciplinary study team proposes a basic experimental study in humans using a remotely delivered group behavioral weight loss intervention to evoke and study plateau physiology. Real-time remote monitoring of weight loss trajectories will be used to individualize assessments for 130 adults with overweight or obesity to occur at baseline, during active weight loss, and at a weight loss plateau. Intensive phenotyping will include serial behavioral assessments and tasks, fasting and postprandial blood sampling, functional and structural brain magnetic resonance imaging, indirect calorimetry, and adipose and muscle biopsies to investigate the contribution of mitochondrial function and other pathways to this weight loss plateau. Future work will probe underlying mechanisms that trigger plateau physiology in a tissue-specific manner, using identified predictors to target individuals and timepoints. In sum, the proposed research uses an innovative, individualized approach to improve understanding of the physiological factors that make additional weight loss difficult once a weight loss plateau is reached. The long-term goal is to develop new approaches for extending weight loss and improving weight maintenance.
肥胖症治疗的行为策略可靠地导致体重减轻和健康益处。但是,在这方面, 体重减轻通常在总体重的约7-10%处达到平台(平台期),之后体重恢复是 常见的,限制了大多数干预策略的能力,以改变肥胖相关疾病的风险, 方式克服这些限制需要进一步了解代谢,食欲, 神经因素抵消并最终阻止体重减轻。现有文献表明, 失去会引起食欲的适应,包括饥饿感的增加和饱腹感的减少。调查 研究小组的初步数据进一步证明,大脑中控制奖励的区域的饱腹感反应受损, 减肥后的动力。记录在案的减肥代谢反应包括全身 和静息能量消耗以及肌肉和脂肪组织中代谢效率的增加。我们 现在,我们使用线粒体代谢的新方法提供了初步数据,表明体重减轻 高原期的特征是外周血单核细胞中线粒体代谢能力的降低。 细胞这项拟议中的研究旨在:1)测试非自愿减肥平台期是否与其他 通过多种组织类型的细胞生物能量学改变的体重减轻阶段,包括循环 血细胞、肌肉和脂肪组织; 2)测试与降低的饱腹感一致的神经生理学变化, 非自愿减肥平台,并评估其与代谢变化的关系; 3)调查 使用基线和行为体重测量期间真实的时间收集的数据预测体重减轻平台期 损失为了解决这三个具体目标,多学科研究小组提出了一个基本的实验 在人类中进行的一项研究,使用远程传递的群体行为减肥干预, 高原生理学实时远程监测减肥轨迹将用于个性化 对130名超重或肥胖的成年人进行基线、主动减肥期间和 减肥平台期强化表型分析将包括系列行为评估和任务,禁食和 餐后采血,功能和结构脑磁共振成像,间接量热法, 以及脂肪和肌肉活检,以研究线粒体功能和其他途径的贡献 到这个减肥平台期。未来的工作将探索触发高原生理学的潜在机制, 组织特异性的方式,使用确定的预测目标个人和时间点。总而言之,拟议的 研究使用创新的,个性化的方法来提高对生理因素的理解, 一旦达到减肥平台期,就很难再减肥。长期目标是发展 延长减肥和改善体重维持的新方法。

项目成果

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Marian L Neuhouser其他文献

Investigating the impact of body composition on the estimation of resting metabolic rate: new equations for adults aged ≥65 years developed using cross-sectional data
探究身体成分对静息代谢率估算的影响:利用横断面数据推导出适用于65岁及以上成年人的新公式
  • DOI:
    10.1016/j.ajcnut.2024.12.023
  • 发表时间:
    2025-04-01
  • 期刊:
  • 影响因子:
    6.900
  • 作者:
    Judi Porter;Leigh C Ward;Kay Nguo;Zoe Davidson;Simone Gibson;Ross Prentice;Marian L Neuhouser;Helen Truby
  • 通讯作者:
    Helen Truby
Energy intake is associated with dietary macronutrient densities: inversely with protein and monounsaturated fat and positively with polyunsaturated fat and carbohydrate among postmenopausal females
在绝经后女性中,能量摄入与膳食常量营养素密度相关:与蛋白质和单不饱和脂肪呈负相关,与多不饱和脂肪和碳水化合物呈正相关
  • DOI:
    10.1016/j.ajcnut.2025.03.011
  • 发表时间:
    2025-05-01
  • 期刊:
  • 影响因子:
    6.900
  • 作者:
    Ross L Prentice;Aaron K Aragaki;Cheng Zheng;JoAnn E Manson;Lesley F Tinker;Dale A Schoeller;Michele N Ravelli;Daniel Raftery;GA Nagana Gowda;Sandi L Navarro;Ying Huang;Yasmin Mossavar-Rahmani;Robert B Wallace;Karen C Johnson;Johanna W Lampe;Marian L Neuhouser
  • 通讯作者:
    Marian L Neuhouser

Marian L Neuhouser的其他文献

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{{ truncateString('Marian L Neuhouser', 18)}}的其他基金

Red and Processed Meat Effects on the Metabolome and Microbiome
红肉和加工肉对代谢组和微生物组的影响
  • 批准号:
    10191413
  • 财政年份:
    2021
  • 资助金额:
    $ 78.91万
  • 项目类别:
Red and Processed Meat Effects on the Metabolome and Microbiome
红肉和加工肉对代谢组和微生物组的影响
  • 批准号:
    10407996
  • 财政年份:
    2021
  • 资助金额:
    $ 78.91万
  • 项目类别:
Red and Processed Meat Effects on the Metabolome and Microbiome
红肉和加工肉对代谢组和微生物组的影响
  • 批准号:
    10596229
  • 财政年份:
    2021
  • 资助金额:
    $ 78.91万
  • 项目类别:
Eating frequency and its influence on satiety and biomarkers of health & disease
饮食频率及其对饱腹感和健康生物标志物的影响
  • 批准号:
    8798420
  • 财政年份:
    2014
  • 资助金额:
    $ 78.91万
  • 项目类别:
Eating frequency and its influence on satiety and biomarkers of health & disease
饮食频率及其对饱腹感和健康生物标志物的影响
  • 批准号:
    8932683
  • 财政年份:
    2014
  • 资助金额:
    $ 78.91万
  • 项目类别:
Eating frequency and its influence on satiety and biomarkers of health & disease
饮食频率及其对饱腹感和健康生物标志物的影响
  • 批准号:
    9102198
  • 财政年份:
    2014
  • 资助金额:
    $ 78.91万
  • 项目类别:
Eating frequency and its influence on satiety and biomarkers of health & disease
饮食频率及其对饱腹感和健康生物标志物的影响
  • 批准号:
    9314567
  • 财政年份:
    2014
  • 资助金额:
    $ 78.91万
  • 项目类别:
Interaction of Vitamin D & Vitamin A with Lung Cancer Risk in Non-Smoking Females
维生素 D 的相互作用
  • 批准号:
    8601154
  • 财政年份:
    2013
  • 资助金额:
    $ 78.91万
  • 项目类别:
Infrastructure Support and Pilot Tissue Collection for the CARET Biorepository
CARET 生物样本库的基础设施支持和试点组织采集
  • 批准号:
    10374863
  • 财政年份:
    2013
  • 资助金额:
    $ 78.91万
  • 项目类别:
Interaction of Vitamin D & Vitamin A with Lung Cancer Risk in Non-Smoking Females
维生素 D 的相互作用
  • 批准号:
    8443600
  • 财政年份:
    2013
  • 资助金额:
    $ 78.91万
  • 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
  • 资助金额:
    $ 78.91万
  • 项目类别:
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Enhancing Energy Expending Adipocytes in White Adipose Tissue
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  • 批准号:
    8827438
  • 财政年份:
    2014
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    $ 78.91万
  • 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:
    $ 78.91万
  • 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:
    $ 78.91万
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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:
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  • 资助金额:
    $ 78.91万
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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:
    $ 78.91万
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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:
    8629741
  • 财政年份:
    2013
  • 资助金额:
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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
  • 批准号:
    23700778
  • 财政年份:
    2011
  • 资助金额:
    $ 78.91万
  • 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:
    $ 78.91万
  • 项目类别:
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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
  • 批准号:
    7610781
  • 财政年份:
    2007
  • 资助金额:
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