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）：大约5900万美国成年人被归类为肥胖，体重指数（BMI）大于30 kg/m2。与肥胖相关的严重心脏代谢健康威胁（例如糖尿病、心脏病、中风）威胁着约30%的美国人口。老龄化人口可能面临特别的风险，因为预计超过50%的中年人体重会增加。有趣的是，在昼夜节律不正常的人群（例如夜班工人和其他健康的不吃早餐的人）中也观察到体重过度增加和代谢紊乱风险增加。研究昼夜节律、衰老和体重之间的相互作用是一种新的探索途径。从广义上讲，该提案研究了导致老龄化和昼夜节律失调人群体重增加的环境和遗传相互作用，以及可能的预防治疗干预措施。 具体而言，该提议利用了创新的环境协议（即去代谢喂养，DF），其导致昼夜光周期和代谢表达之间的不对准。然后将这种环境干预应用于不同年龄的遗传模型（即C57 BL/6 J和Clock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，该提案调查了三个具体的假设：1）年龄和DF叠加影响能量消耗，2）年龄可以夸大DF期间的代谢损伤，3）DF改变昼夜节律钟和脑和外周组织中的代谢基因表达。该提案的目标可以通过严格的研究培训计划来实现，该计划侧重于整合分子技术，遗传学以及体重和代谢的生理测量。 该提案旨在揭示导致体重增加的新机制，预计将导致新的见解和治疗方法，用于治疗和预防所有年龄组以及昼夜节律失调人群中的肥胖症，糖尿病和其他心脏代谢疾病。 公共卫生关系： 这一建议有望带来新的见解和治疗方法，用于治疗和预防肥胖症、糖尿病和其他心脏代谢疾病，老年人和昼夜节律失调的人群尤其容易受到这些疾病的影响。