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：
Marian L Neuhouser
金额：
$ 78.91万
依托单位：
UNIVERSITY OF WASHINGTON
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

来源：
https://reporter.nih.gov/project-details/10734323
关键词：
Address Adipocytes Adipose tissue Adult Behavior Therapy Behavior assessment Behavioral Bioenergetics Biological Biology Biopsy Blood Cells Blood specimen Body Weight Body Weight decreased Brain Brain region Clinical Research Data Desire for food Diet Eating Eating Behavior Energy Metabolism Fasting Functional Magnetic Resonance Imaging Future Goals Health Health Benefit Hormones Human Impairment Indirect Calorimetry Individual Intervention Investigation Knowledge Liquid substance Literature Maintenance Measures Metabolic Metabolism Mitochondria Monitor Motivation Muscle Neurologic Obesity Obesity associated disease Outcome Outcome Assessment Overweight Participant Pathway interactions Peripheral Blood Mononuclear Cell Phase Phenotype Physiological Physiological Adaptation Physiology Pre-Clinical Model Predictive Factor Reliability of Results Research Rest Rewards Satiation Satiety Response Skeletal Muscle Specimen Structure Technology Testing Time Tissue Sample Tissues Visit Weight Work brain magnetic resonance imaging design disorder risk experimental study human tissue improved increased appetite innovation mitochondrial metabolism multidisciplinary neurophysiology novel novel strategies obesity treatment personalized approach real time monitoring remote delivery remote monitoring respiratory response weight loss intervention weight maintenance

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.

肥胖治疗的行为策略可靠地导致体重减轻和健康益处。然而，体重减轻通常在体重总体重（高原阶段）的〜7-10％之后保持重量常见，限制大多数干预策略在持续的方式。克服这些局限性需要提高对代谢，食欲和抵消并最终停止的神经系统因素。现有文献表明体重损失唤起了食欲适应，包括增加饥饿和增加的饱腹感。调查团队的初步数据增加了证据，表明控制奖励和动机遵循体重减轻。对减肥的代谢反应包括总体下降以及静止的能量消耗以及提高肌肉和脂肪组织的代谢效率。我们现在，使用线粒体代谢的新型测量表明体重减轻高原的特征是外周血单核中线粒体代谢能力的降低细胞。拟议的研究目的是1）测试是否有非自愿减肥高原与其他区分开通过改变多种组织类型的细胞生物能量的改变，包括循环的阶段血细胞，肌肉和脂肪组织； 2）测试神经生理学的变化与饱腹感一致邀请减肥高原和评估其与新陈代谢变化的关系； 3）调查使用基线和行为重量实时收集的数据预测减肥高原的预测因素损失。为了解决这三个特定目标，多学科研究团队提出了一个基本的实验使用远程交付的群体行为减肥干预措施在人类中进行研究，以唤起和研究高原生理学。实时远程减肥轨迹将用于个性化评估130名超重或肥胖症的成年人在基线，主动减肥期间和减肥高原。密集表型将包括串行行为评估和任务，禁食和餐后抽样，功能和结构性脑磁共振成像，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对于这个减肥高原。未来的工作将探究触发高原生理学的基本机制组织特异性的方式，使用确定的预测因子来靶向个体和时间点。总而言之研究使用一种创新的个性化方法来提高对物理因素的理解一旦达到减肥高原，使额外的体重减轻变得困难。长期目标是发展扩大体重减轻和改善体重维持的新方法。