Predictors of Recidivism to Obesity in Weight-Reduced Individuals

体重减轻者肥胖累犯的预测因素

• 批准号: 10571766
• 负责人: DYMPNA GALLAGHER
• 金额: $ 122.79万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-24 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10571766
• 关键词: Accounting; Achievement; Adipocytes; Adipose tissue; Autonomic nervous system; Behavioral; Biochemical; Body Composition; Body Weight; Body Weight decreased; Body fat; Brain; Brain Diseases; Calibration; Catecholamines; Circadian Rhythms; Clinical; Communities; Complex; Consensus; Corpus striatum structure; Data; Development; Diabetes Mellitus; Dorsal; Dose; Dyslipidemias; Eating; Eating Behavior; Endocrine; Energy Intake; Energy Metabolism; Environment; Environmental Impact; Epigenetic Process; Equation; Fatty Liver; Food; Functional Magnetic Resonance Imaging; Gene Expression; Health Care Costs; Heart Diseases; Home environment; Homeostasis; Human; Hunger; Hypertension; Individual; Individual Differences; Intervention; Leptin; Life Style; Maintenance; Malignant Neoplasms; Measures; Mediating; Medical; Metabolic; Metabolism; Mitochondria; Molecular; Morbidity - disease rate; Muscle; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Overweight; Peptides; Peripheral Blood Mononuclear Cell; Persons; Phenotype; Physics; Physiological; Physiological Adaptation; Physiological Processes; Physiology; Plasma; Procedures; Prospective Studies; Protocols documentation; Respiration; Role; SARS-CoV-2 infection; Severities; Site; Skeletal Muscle; Sleep; Standardization; Surveys; System; Task Performances; Thinness; Thyroid Gland; Time; Training; Weight; base; design; endophenotype; energy balance; food environment; in vivo; instrument; mathematical model; metabolomics; mortality; nanoelectromechanical system; novel; nutrition; physiologic model; prospective; recidivism; response; success; urinary; weight maintenance

Obesity is a major contributor to human illness and health care costs by virtue of its functional associations with type 2 diabetes, hypertension, fatty liver, dyslipidemias, various cancers, degenerative brain disease and, very recently, contribution to morbidity and mortality associated with SARS-CoV-2 infection. Modest weight loss can mitigate the severity – or entirely reverse - many of these phenotypes. Maintenance of a 10% reduced body in obese or lean individuals invokes homeostatic changes in energy expenditure (decreased) and hunger (increased) that tend to restore body weight. These changes are conveyed by persistent complex molecular- physiological processes in the brain and autonomic nervous systems, thyroid and leptin axes, skeletal muscle, and adipose tissue. Individuals differ in the intensity of these responses, perhaps accounting for differences in long-term success for weight loss maintenance. This study prospectively examines the behavioral and molecular physiology of these systems following a lifestyle-mediated 10% weight reduction in individuals with overweight or obesity, and examines the contributions of these factors to amount of weight regain in the one year period following achievement of the weight reduction during a period of minimum clinical intervention. Our Specific Experimental Aims are to: 1. Examine the behavioral, metabolic, and environmental impacts on success in sustaining 10% weight loss by measuring the association of (a) ad lib energy intake (EI), (b) 24h energy expenditure (EE); and (c) the individual’s food environment at reduced body weight on changes in body weight and fat mass one year following achievement of 10% weight reduction. 2. Assess the physiology of the weight-reduced state in dynamic circumstances in order to provide predictors of weight outcome at 12 months after 10% weight loss. EI and EE will be measured: (a) in response to a single dose of leptin administered after achievement of reduced body weight; (b) 6 months following weight loss. 3. Generate mechanistically-informed regression equations predicting change in body weight in the 12 months following 10% weight loss. “Endophenotypes” related to EI and EE will be measured in the weight- reduced state: food-choice task performance associated with food intake and fMRI activity in the dorsal striatum; sleep/circadian rhythms; skeletal muscle contractile efficiency (in vivo and ex vivo), plasma metabolomics /exposomics and endocrines, urinary catecholamines, gene expression and epigenetics of adipose tissue and muscle, and peripheral blood mononuclear cells. These endophenotypes, EI and EE, will be used to generate predictive equations that will quantify the relative contributions of these factors and suggest possible interventions to assist in long-term maintenance of reduced body weight.

肥胖是人类疾病和医疗保健成本的主要因素，其功能关联 2型糖尿病，高血压，脂肪肝，血脂异常，各种癌症，退化性脑疾病以及非常非常 最近，对与SARS-COV-2感染相关的发病率和死亡率的贡献。减肥可以 减轻这些表型的严重程度（或完全逆转）。维持减少10％的身体 肥胖或精益人士调用能量消耗的体内平衡变化（减少）和饥饿 （增加）倾向于恢复体重。这些变化是通过持续的复合物分子传达的 大脑和自主神经系统的生理过程，甲状腺和瘦素轴，骨骼肌， 和脂肪组织。个人在这些反应的强度方面有所不同，也许是考虑到差异 减肥维持的长期成功。这项研究前瞻性地检查了行为和分子 在生活方式介导的超重患者的生活方式介导的10％体重下，这些系统的生理学 或肥胖，检查这些因素对体重量的贡献保留在一年中 在最小临床干预期间减轻体重后。我们的具体 实验目的是： 1。检查行为，代谢和环境对维持10％体重减轻的成功的影响 通过测量（a）aD lib能量摄入（EI），（b）24h能量消耗（EE）的关联； （c） 个人的食物环境减轻体重的体重变化和脂肪质量的变化一年 达到10％的体重减轻后。 2。在动态情况下评估减轻体重降低状态的生理学，以提供预测因子 体重减轻后12个月的体重结局。将测量EI和EE：（a）响应A 达到体重减轻后，单剂量的瘦素； （b）体重后6个月 损失。 3。生成机械信息的回归方程，可预测12个体重的变化 减肥10％后的几个月。与EI和EE相关的“内表型”将在重量中测量 降低的状态：与食物摄入量相关的食物选择任务性能和背面的fMRI活动 纹状体；睡眠/昼夜节律；骨骼肌肉收缩效率（体内和离体），血浆 代谢组学 /杂种学和内分泌，尿catecholamines，基因表达和表观遗传学 脂肪组织和肌肉以及外周血单核细胞。这些内表型，EI和EE， 将用于生成预测方程，以量化这些因素的相对贡献和 提出可能采取的干预措施，以帮助长期维持体重减轻。