Metabolic Adaptations to Two Year Caloric Restriction

对两年热量限制的代谢适应

• 批准号: 7364619
• 负责人: Eric Ravussin
• 金额: $ 109.46万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7364619
• 关键词: Address; Adipose tissue; Adrenal Glands; Adult; Affect; Aging; Animal Model; Autonomic nervous system; Behavioral; Birth; Body Temperature; Body Weight; Body Weight decreased; Caloric Restriction; Candidate Disease Gene; Carbohydrates; Cardiovascular Diseases; Cardiovascular system; Chronic; Chronic Disease; Circadian Rhythms; DNA; Diabetes Mellitus; Disease; Drops; Eating Disorders; Endocrinologist; Energy Intake; Energy Metabolism; Exercise; Food; Gene Expression; Hemostatic function; Homocysteine; Homocystine; Human; Hypothalamic structure; Inflammation; Insulin; Investigation; Leptin; Life; Lipids; Longevity; Lower Organism; Macaca mulatta; Maintenance; Measurement; Measures; Metabolic; Metabolic Diseases; Metabolism; Molecular; Moods; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Overweight; Oxidative Stress; Physical Fitness; Physical activity; Primates; Production; Proteins; Psychologist; Quality of life; Rate; Reaction Time; Records; Relative (related person); Rest; Risk; Risk Factors; Rodent; Signal Transduction; Single-Blind Study; Skeletal Muscle; Surrogate Markers; Sympathetic Nervous System; Testing; Thyroid Function Tests; Tissues; age related; cardiovascular disorder risk; cognitive function; diabetes risk; energy balance; fitness; improved; interest; longevity gene; mortality; multidisciplinary; neuronal cell body; nonhuman primate; protein metabolism; repaired; research study; response; sedentary; sensory neuron specific sodium channel; size; volunteer; Address; Adipose tissue; Adrenal Glands; Adult; Affect; Aging; Animal Model; Autonomic nervous system; Behavioral; Birth; Body Temperature; Body Weight; Body Weight decreased; Caloric Restriction; Candidate Disease Gene; Carbohydrates; Cardiovascular Diseases; Cardiovascular system; Chronic; Chronic Disease; Circadian Rhythms; DNA; Diabetes Mellitus; Disease; Drops; Eating Disorders; Endocrinologist; Energy Intake; Energy Metabolism; Exercise; Food; Gene Expression; Hemostatic function; Homocysteine; Homocystine; Human; Hypothalamic structure; Inflammation; Insulin; Investigation; Leptin; Life; Lipids; Longevity; Lower Organism; Macaca mulatta; Maintenance; Measurement; Measures; Metabolic; Metabolic Diseases; Metabolism; Molecular; Moods; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Overweight; Oxidative Stress; Physical Fitness; Physical activity; Primates; Production; Proteins; Psychologist; Quality of life; Rate; Reaction Time; Records; Relative (related person); Rest; Risk; Risk Factors; Rodent; Signal Transduction; Single-Blind Study; Skeletal Muscle; Surrogate Markers; Sympathetic Nervous System; Testing; Thyroid Function Tests; Tissues; age related; cardiovascular disorder risk; cognitive function; diabetes risk; energy balance; fitness; improved; interest; longevity gene; mortality; multidisciplinary; neuronal cell body; nonhuman primate; protein metabolism; repaired; research study; response; sedentary; sensory neuron specific sodium channel; size; volunteer

DESCRIPTION: (provided by applicant) Calorie restriction (CR) is known to extend the lifespan of rodents and several ?lower? species, and to improve surrogate markers for longevity and mortality in rhesus monkeys. There is, however, a paucity of reliable information on whether this is the case in humans as well. In response to a specific RFA from the NIA for descriptive experiments to address this issue, we propose a controlled, single-blinded study of several adaptive responses pertinent to this question in overweight volunteers imposed an initial 25% negative energy balance for two years by CR alone or by CR with additional physical activity. These responses include changes in energy metabolism, surrogate markers of oxidative stress and risks for cardiovascular disease and type-2 diabetes mellitus, neuroendocrine functions and autonomic nervous system activity, expression of candidate genes involved in energy metabolism, oxidative stress and longevity, and quality of life and physical fitness. In addition to descriptive information, we will test the hypotheses that CR with weight loss and maintenance of energy balance at a new body weight: 1. Lowers absolute and relative rates of energy expenditure and body temperature and decreases evidence of tissue oxidative stress. 2. Improves surrogate markers for cardiovascular disease and type-2 diabetes mellitus. 3. Affects the diurnal secretion of leptin leading to adaptations in the neuroendocine and autonomic nervous system enhance soma maintenance. 4. Alters the expression of genes involved in energy/protein metabolism, the production and clearance of reactive species, and ?longevity? genes in a fashion consistent with animal models of CR. 5. Improves the quality of life and metabolic fitness. A multidisciplinary team, including physiologists, behavioral psychologists, endocrinologists, molecular biologists and geneticists will conduct this study.

描述：（由申请人提供）卡路里限制（CR）已知 延长啮齿动物的寿命和几个？物种，并改善 恒河猴的寿命和死亡率的替代标记。有， 但是，很少关于这种情况的可靠信息 人类也是如此。响应NIA的特定RFA以进行描述 解决此问题的实验，我们提出了一个受控的单盲 在超重中研究与这个问题有关的几个自适应反应 志愿者通过CR实施了两年的初始25％负能量平衡 单独或进行额外的体育锻炼。这些响应包括 能量代谢的变化，氧化应激的替代标记和风险的变化 用于心血管疾病和2型糖尿病，神经内分泌 功能和自主神经系统活动，候选基因的表达 参与能量代谢，氧化应激和寿命以及质量 生活和身体健康。除了描述性信息外，我们还将测试 在体重减轻和能源平衡维持的假设 新体重： 1。降低能量消耗的绝对和相对速率 温度并降低组织氧化应激的证据。 2。改善心血管疾病和2型糖尿病的替代标记 Mellitus。 3。影响瘦素的昼夜分泌，导致适应 神经内政量和自主神经系统可增强SOMA维护。 4。改变参与能量/蛋白质代谢的基因的表达， 反应性物种的生产和清除以及？寿命？基因 时尚与Cr的动物模型一致。 5。提高生活质量和代谢健身。 一个多学科团队，包括生理学家，行为心理学家， 内分泌学家，分子生物学家和遗传学家将进行这项研究。