Body Composition, Energetics, and Longevity

身体成分、能量和寿命

• 批准号: 7783177
• 负责人: DAVID B ALLISON
• 金额: $ 39.79万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7783177
• 关键词: Abbreviations; Accounting; Address; Adipocytes; Adipose tissue; Adverse effects; Affect; Aging; American; Anatomy; Animal Model; Animals; Arts; Back; Basic Science; Behavioral; Benchmarking; Biology; Blood; Body Composition; Body Weight; Body Weight decreased; Body Weights and Measures; Body fat; Caloric Restriction; Calorimetry; Cardiovascular Diseases; Cause of Death; Clinical; Clinical Research; Complement; Data; Data Analyses; Development; Diet; Disease; Ensure; Epidemiologic Studies; Epidemiology; Ethics; Fat-Restricted Diet; Fatty acid glycerol esters; Female; Future; Gene Expression; Genes; Goals; Grant; Human; Individual; Inflammation; Insulin Resistance; Intake; Intention; Intervention; Joints; Laboratories; Laboratory Animals; Life; Literature; Long-Term Effects; Longevity; Magnetic Resonance; Malignant Neoplasms; Measurement; Measures; Mediating; Mediation; Mediator of activation protein; Metabolic; Methods; Modeling; Morbid Obesity; Morbidity - disease rate; Morphology; Mus; Nature; Non-Insulin-Dependent Diabetes Mellitus; Non-Visceral; Obese Mice; Obesity; Operative Surgical Procedures; Organism; Pathway interactions; Physiological; Prevalence; Protocols documentation; Public Health; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Recommendation; Relative (related person); Research; Research Design; Risk Factors; Rodent; Rodent Model; Role; Sample Size; Sampling; Sampling Studies; Staging; Strategic Planning; Test Result; Testing; Time; United States National Institutes of Health; Ursidae Family; Vertebrates; Visceral; Weight; Work; Writing; X-Ray Computed Tomography; animal facility; bariatric surgery; base; design; experience; feeding; hazard; human subject; in vivo; inflammatory marker; male; moderate obesity; mortality; public health relevance; research study; theories

DESCRIPTION (provided by applicant): Although caloric restriction is known to prolong life and obesity is known to shorten life in many species including many mammalian species, many questions remain unanswered at both the level of basic biology and the public health/clinical level. For practical, theoretical, and ethical reasons it is impossible to randomly assign humans to different levels of body weight, fatness, or fat distribution or different degrees of weight stability and to then follow them for the entire lifespan. Yet, questions about the effects of such body weight and composition variables remain. Model organism studies are a key aspect of the totality of evidence that can be brought to bear on such questions by offering rigorously controlled full-lifespan experiments that can complement other types of studies that can be done in humans. The research proposed addresses questions such as: Among obese organisms, must weight loss be sustained to be beneficial with respect to lifespan? Are repeated bouts of weight loss and regain (i.e., 'weight cycling') beneficial, harmful, or neutral? To what extent do the beneficial effects of weight loss among obese organisms result from reductions in total fat, visceral fat, metabolic rate, or adipocyte size. These questions will be addressed in a randomized lifespan experiment in dietary obese mice using state-of-the-art body composition, metabolic assessment, and statistical analysis methods, supplemented with small targeted mechanistic sub-studies. These questions have implications for basic science in terms of opening and prioritizing pathways to explore as mediators of the salubrious effects of weight loss and caloric restriction and implications for strengthening, weakening, or refining clinical recommendations concerning the types of behavioral and anatomic alterations likely to enhance longevity among obese humans. PUBLIC HEALTH RELEVANCE: Over 50 million Americans are obese and are therefore predicted to live less long than they would otherwise live. Whether reductions in overall obesity or selected aspects of fatness among obese persons will prolong life remains the subject of active debate and controversy. The proposed research will help provide information to inform that dialogue.

描述（由申请人提供）：尽管已知热量限制会延长寿命和肥胖症在包括许多哺乳动物物种在内的许多物种中的寿命缩短，但许多问题在基本生物学和公共卫生/临床水平的水平上均未得到解决。出于实践，理论和道德原因，不可能将人类随机分配给不同水平的体重，脂肪或脂肪分布或不同程度的体重稳定性，然后在整个寿命中跟随它们。然而，仍然存在有关这种体重和组成变量影响的问题。模型有机体研究是通过提供严格控制的全氟化器实验，可以补充可以在人类中可以进行的其他类型的研究，这是可以在此类问题上带来的大量证据的关键方面。拟议的研究提出了诸如诸如：在肥胖生物中，减肥必须维持对寿命有益的问题吗？重复体重减轻并恢复（即“体重骑自行车”）有益，有害或中立？肥胖生物体重减轻的有益影响在多大程度上是由于总脂肪，内脏脂肪，代谢率或脂肪细胞大小的减少而导致的。这些问题将在饮食肥胖小鼠的随机寿命实验中使用最先进的身体组成，代谢评估和统计分析方法，并补充了针对小的靶向机械基础研究。这些问题对基础科学具有开放性和优先级别探索途径的意义，以作为减肥和热量限制的调解人，以及对加强，削弱或完善有关行为和解剖学变化类型的临床建议的影响，对肥胖人类的行为和解剖学变化的类型。 公共卫生相关性：超过5000万美国人肥胖，因此预计寿命的长度比他们原本的寿命少。肥胖者中肥胖的总体肥胖症还是肥胖的某些方面是否会延长寿命仍然是主动辩论和争议的主题。拟议的研究将有助于提供信息以告知对话。