Aging and meal timing interact to exaggerate weight gain

衰老和进餐时间相互作用导致体重增加

• 批准号: 8003810
• 负责人: Deanna Marie Arble
• 金额: $ 3.33万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003810
• 关键词: Adult; Affect; Age; Aging; American; Body Weight; Body mass index; Brain; Circadian Rhythms; Diabetes Mellitus; Disease; Energy Metabolism; Gene Expression; Genetic; Genetic Models; Genetic Techniques; Goals; Health; Heart Diseases; Impairment; Lead; Light; Link; Measurement; Metabolic; Metabolic Diseases; Metabolism; Molecular; Mutant Strains Mice; Obesity; Peripheral; Physiological; Population; Prevention; Protocols documentation; Research Training; Risk; Stroke; Therapeutic; Therapeutic Intervention; Time; Tissues; Weight; Weight Gain; age group; aged; aging population; circadian pacemaker; environmental intervention; feeding; gene environment interaction; innovation; insight; middle age; obesity prevention; public health relevance; shift work; therapy design

DESCRIPTION (provided by applicant): About 59 million American adults are classified as obese, with a body mass index (BMI) greater than 30 kg/m2. Serious cardiometabolic health threats linked to obesity (e.g. diabetes, heart disease, stroke) threaten about 30% of the American population. The aging population may be at particular risk, as over 50% of middle aged adults are expected to gain excess weight. Interestingly, excess weight gain and an increased risk for metabolic disorders is also observed in the circadian desynchronized population (e.g. night shift workers and otherwise healthy, non-breakfast eaters). Investigating the interaction between circadian rhythms, aging and body weight is a new avenue for exploration. Broadly, this proposal studies the environmental and genetic interactions which lead to weight gain in the aging and circadian desynchronized population and possible therapeutic interventions for its prevention. Specifically, this proposal utilizes an innovative, environmental protocol (i.e. desynchronized feeding, DF) which causes a misalignment between the circadian light cycle and metabolic expression. This environmental intervention is then applied to genetic models (i.e. C57BL/6J and Clock mutant mice) of varying ages to determine the gene-environment interactions leading to weight gain associated with age and DF. Using this approach, this proposal investigates three specific hypotheses: 1) that age and DF additively affect energy expenditure, 2) that age can exaggerate metabolic impairments during DF, and 3) that DF alters circadian clock and metabolic gene expression in brain and peripheral tissues. The goals of this proposal can be achieved through a rigorous research training plan which focuses on integrating molecular techniques, genetics, and physiological measurements of body weight and metabolism. This proposal aims to uncover new mechanisms leading to weight gain and is expected to lead to new insights and therapeutic approaches designed for the treatment and prevention of obesity, diabetes and other cardiometabolic disorders all age groups as well as in the circadian desynchronized population. PUBLIC HEALTH RELEVANCE: This proposal is expected to lead to new insights and therapeutic approaches designed for the treatment and prevention of obesity, diabetes and other cardiometabolic disorders in which the aged and circadian desynchronized population are particularly vulnerable.

描述（由申请人提供）：约有5900万美国成年人被归类为肥胖，体重指数（BMI）大于30 kg/m2。严重的心脏代谢健康威胁与肥胖有关（例如糖尿病，心脏病，中风）威胁着约30％的美国人群。老龄化的人口可能有特殊的风险，因为预计超过50％的中年成年人会增加体重过多。有趣的是，在昼夜节日的人群中也观察到体重增加和代谢性疾病的风险增加（例如夜班工人和其他健康的非短饮食者）。研究昼夜节律，体重和体重之间的相互作用是探索的新途径。从广义上讲，该提议研究了环境和遗传相互作用，从而导致体重增加，而昼夜节律的人群的体重增加以及预防的可能治疗干预措施。 具体而言，该建议利用创新的环境方案（即脱离喂养，DF），这会导致昼夜节律光周期和代谢表达之间的错位。然后将这种环境干预应用于不同年龄的遗传模型（即C57BL/6J和时钟突变小鼠），以确定导致与年龄和DF相关的体重增加的基因环境相互作用。使用这种方法，该提案研究了三个特定的假设：1）年龄和DF添加性影响能量消耗，2）年龄可以夸大DF期间的代谢障碍，而3）DF会改变昼夜节律时钟和外围组织中的代谢基因的表达。该提案的目标可以通过严格的研究培训计划来实现，该计划的重点是整合体重和代谢的分子技术，遗传学和生理测量。 该提案旨在揭示导致体重增加的新机制，并有望导致新的见解和治疗方法，旨在治疗和预防肥胖，糖尿病和其他心脏代谢障碍所有年龄段以及在昼夜节律的人群中。 公共卫生相关性： 预计该提案将导致新的见解和治疗方法，旨在治疗和预防肥胖，糖尿病和其他心脏代谢性疾病，其中年龄和昼夜节律不同步人群特别容易受到攻击。