Physiological changes underlying the weight loss plateau in humans

人类减肥平台期的生理变化

• 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
• 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

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。然而，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名超重或肥胖成年人在基线、主动减肥期间和治疗期间进行评估 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。