Diurnal rhythm in nutrient metabolism for metabolic homeostasis

营养代谢的昼夜节律促进代谢稳态

• 批准号: 9923646
• 负责人: Satchidananda Panda
• 金额: $ 67.34万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-10 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9923646
• 关键词: ARNTL gene; Animal Model; Animals; Attenuated; Behavioral; Body Weight; Cardiovascular Diseases; Chronic; Circadian Dysregulation; Circadian Rhythms; Circadian desynchrony; Combined Modality Therapy; Complex; Consumption; Diabetes Mellitus; Diet; Disease; Diurnal Rhythm; Eating; Endocrine; Environment; Environmental Impact; Etiology; Exhibits; Fasting; Foundations; Future; Gene Expression; General Population; Genes; Genetic; Genetic Models; Genotype; Health; Hepatic; High Fat Diet; Homeostasis; Hour; House mice; Human; Hyperlipidemia; Incidence; Insecta; Insulin Resistance; Intervention; Jet Lag Syndrome; Knock-out; Light; Link; Liver; Measures; Mediating; Messenger RNA; Metabolic; Metabolic Diseases; Metabolism; Methods; Modeling; Molecular; Mus; Mutant Strains Mice; Nature; Nutrient; Obesity; Organ; Pathway interactions; Pattern; Phase; Physiology; Plant Roots; Populations at Risk; Prevention; Prevention therapy; Regulation; Role; Schedule; Sleep; System; Testing; Therapeutic; Time; Time-restricted feeding; Transcript; Translations; Wakefulness; Weight Gain; Wild Type Mouse; Work; attenuation; blood glucose regulation; cardiometabolism; circadian; circadian pacemaker; circadian regulation; cohort; combat; epidemiology study; experimental study; feeding; gene function; human model; improved; metabolic phenotype; nonalcoholic steatohepatitis; novel; nutrient metabolism; nutrition; obesity risk; prevent; protein metabolite; public health relevance; shift work; time interval; transcriptome

Abstract Disruption in metabolic homeostasis is increasingly recognized as the root cause of obesity, insulin resistance, nonalcoholic steatohepatitis, hyperlipidemia, and cardiovascular diseases. Current efforts on prevention and therapies are focused on key components that mediate nutrient utilization, interconversion and storage. However, metabolic diseases are complex in nature with disruption in multiple pathways, often requiring progressively more complex combination therapies. Novel intervention that is effective both as a preventative method and to augment therapy is urgently needed. The circadian regulation of metabolism and physiology offer a novel promising avenue for the prevention and the treatment of these diseases. There is growing evidence that disruption of natural circadian rhythm in sleep and nutrition as occurs in people doing shiftwork is associated with increased incidence of metabolic diseases in humans. Furthermore, even among the general population, the daily rhythm of sleep and nutrition is significantly disrupted. Therefore, behavioral changes that sustain robust circadian function are considered to be beneficial against challenges that predispose to metabolic diseases. Time-restricted feeding (TRF), in which animals are fed within an 8-12 hour time interval during their natural circadian wakeful hours is both preventative and therapeutic against metabolic diseases in both mice and insects. There is growing precedence that the time of food intake has a profound impact on body weight regulation in humans. While these preliminary findings are encouraging, major questions remain to be answered before any potential human translation. Is TRF beneficial under a shiftwork paradigm that chronically disrupts circadian rhythm? And what are the potential mechanisms underlying TRF benefits? This proposal will test these questions in mice that are effectively used to model circadian rhythm disruption and metabolic diseases.

摘要 代谢稳态的破坏越来越被认为是肥胖、胰岛素抵抗、 非酒精性脂肪性肝炎、高脂血症和心血管疾病。目前的预防和 治疗的重点是调节营养利用、相互转化和储存的关键成分。 然而，代谢性疾病本质上是复杂的，多个途径被破坏，通常需要 越来越复杂的联合治疗。一种既能有效预防 迫切需要方法和加强治疗。代谢和生理的昼夜节律调节 为预防和治疗这些疾病提供了一种新的有希望的途径。人们越来越 有证据表明，睡眠和营养方面的自然昼夜节律被打乱，就像人们轮班工作一样， 与人类代谢疾病发病率的增加有关。此外，即使在一般 人口，睡眠和营养的日常节奏被大大打乱。因此，行为变化， 持续强有力昼夜节律功能被认为有益于对抗易患 代谢性疾病限时饲喂（TRF），在8 - 12小时的时间间隔内饲喂动物 在他们自然的昼夜节律清醒的时间，是预防和治疗代谢疾病， 包括老鼠和昆虫。越来越多的人认为，食物摄入的时间对 人体的体重调节。虽然这些初步调查结果令人鼓舞，但仍然存在一些重大问题 在任何可能的人工翻译之前得到回答。在轮班工作范例下， 会长期扰乱昼夜节律吗扶轮基金会的潜在效益机制是什么？这 该提案将在小鼠中测试这些问题，这些小鼠有效地用于模拟昼夜节律中断， 代谢性疾病