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: 10190515
• 负责人: DYMPNA GALLAGHER
• 金额: $ 25万
• 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 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10190515
• 关键词: Accounting; Achievement; Adipocytes; Adipose tissue; Adult; 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; Fatty acid glycerol esters; Feeding behaviors; 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; Monitor; Morbidity - disease rate; Muscle; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Outpatients; Overweight; Patients; 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; Signal Transduction; Site; Skeletal Muscle; Sleep; Standardization; Surveys; System; Task Performances; Thinness; Thyroid Gland; Time; Training; Weight; base; design; endophenotype; energy balance; food environment; in vivo; individual response; instrument; lifestyle intervention; mathematical model; metabolomics; mortality; nanoelectromechanical system; novel; nutrition; physiologic model; primary outcome; prospective; recidivism; response; success; urinary; vector; 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费用的一个主要因素，因为它与 2 型糖尿病、高血压、脂肪肝、血脂异常、各种癌症、退行性脑部疾病等 最近，适度的体重减轻可能会导致与 SARS-CoV-2 感染相关的发病率和死亡率。 减轻或完全逆转许多这些表型的严重程度，使身体保持减少 10%。 肥胖或瘦人会引起能量消耗（减少）和饥饿的稳态变化 （增加）往往会恢复体重。这些变化是由持久的复杂分子传递的。 大脑和自主神经系统、甲状腺和瘦素轴、骨骼肌的生理过程， 个体的这些反应的强度有所不同，这可能是造成差异的原因。 这项研究前瞻性地研究了减肥维持的长期成功。 超重个体通过生活方式介导体重减轻 10% 后这些系统的生理学变化 或肥胖，并检查这些因素对一年内体重恢复量的贡献 在我们的具体干预期间实现最低体重减轻后。 实验目的是： 1. 检查行为、代谢和环境对成功维持 10% 体重减轻的影响 通过测量 (a) 随意能量摄入 (EI)、(b) 24 小时能量消耗 (EE) 和 (c) 之间的关联； 体重减轻时个体的食物环境对体重和脂肪量一年变化的影响 体重减轻 10% 后。 2. 评估动态环境下减重状态的生理学，以提供预测因素 将测量 EI 和 EE 减重 10% 后 12 个月时的体重结果： (a) 响应 (b) 体重减轻后 6 个月服用单剂瘦素； 损失。 3. 生成预测 12 岁体重变化的机械回归方程 体重减轻 10% 后的几个月，将在体重中测量与 EI 和 EE 相关的“内表型”。 减少状态：与食物摄入和背侧功能磁共振成像活动相关的食物选择任务表现 纹状体；睡眠/昼夜节律；骨骼肌收缩效率（体内和离体），血浆 代谢组学/暴露组学和内分泌、尿儿茶酚胺、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，量化这些因素的相对贡献， 建议可能的干预措施，以帮助长期维持减轻的体重。