Molecular basis of circadian rhythms disruptions linked cardiometabolic disorders and their mitigation using dietary intervention
昼夜节律紊乱的分子基础与心脏代谢紊乱及其通过饮食干预的缓解
基本信息
- 批准号:10442441
- 负责人:
- 金额:$ 39.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-12-01 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAffectAgeAgingAnimal ModelAttenuatedBehavioralBiological ClocksBiological ModelsCaloric RestrictionCaloriesCardiacCardiac healthCardiometabolic DiseaseCardiovascular DiseasesCardiovascular systemCircadian DysregulationCircadian RhythmsCommunitiesConsumptionDarknessDefectDeteriorationDietDietary InterventionDrosophila genusDrosophila melanogasterEatingEffectivenessEnergy IntakeEnergy MetabolismEtiologyExperimental ModelsFRAP1 geneFastingGene ExpressionGene Expression ProfileGenesGeneticGoalsHealthHeartHeart AbnormalitiesHeart DiseasesHourHumanIncidenceIndustrializationInterventionLifeLife StyleLightLinkLong-Term EffectsMediatingMetabolicMetabolic DiseasesModelingMolecularMolecular GeneticsMonitorMutationMyocardial dysfunctionMyocardiumNutrientObesityOxidative StressPathogenicityPathologicPathway interactionsPatternPerformancePharmacologyPhysiologicalPhysiologyProteinsPublic HealthPublishingRNARestRiskRisk FactorsRoleSamplingSeriesSeveritiesSleepSocietiesStarvationTestingTimeTime-restricted feedingTreatment EfficacyValidationage effectage relatedattenuationbasecardiometabolic riskcircadiancircadian pacemakercomorbiditydetection of nutrientexperimental studyfeedingflyfunctional improvementheart disease riskheart functionhuman old age (65+)improvedknock-downmuscle physiologynovelobesogenicpreventproteostasisresponseshift worksleep patterntime usetool
项目摘要
Project Summary:
Genetic and lifestyle perturbation of the circadian clock trigger cardiovascular diseases. The proposed
study will examine how aging, obesity and circadian rhythm disruptions linked with cardiometabolic disorders,
and how time-restricted feeding (TRF) mitigates these defects. The leading risk factors for cardiometabolic
diseases are age, shift work, energy dense diet and aberrant eating/sleeping patterns. Each of these factors
disrupts circadian rhythms, and it has been shown in model organisms that genetic perturbation of the circadian
clock increases the incidence and severity of cardiac diseases. For example, an aberrant eating pattern in
human, increases the risk of developing cardiovascular diseases by as much as 55%, after controlling for diet
and lifestyle, possibly by disruption of circadian clock. Also, mutations of circadian clock genes prone to cardiac
diseases and light-induced circadian disruptions further deteriorates cardiac abnormalities. Conversely, TRF
paradigm without reducing caloric intake has been shown to prevent various metabolic disorders and attenuates
age-linked cardiac dysfunction. However, pathogenic linkage of circadian clock disruptions with cardiometabolic
diseases, or the potential benefit of TRF intervention has not been assessed at the molecular or genetic level.
Thus, our scientific premise is that factors that affect circadian rhythms offer new avenues to understand the
etiology and attenuation of cardiometabolic disorders.
To address the mechanistic basis of this alarming public health issue, we have developed novel
Drosophila melanogaster (fruit fly) models to mitigate age, obesity and circadian disruption-induced cardiac
disorders by imposing feeding/fasting rhythms with TRF. Drosophila will serve as an excellent model system for
basic discoveries in circadian rhythms, energy metabolism and cardiac muscle physiology. Aim 1 of the proposed
study is to determine the molecular basis of the effectiveness of TRF in delaying age-, obesogenic challenges,
and circadian disruption-induced deterioration of cardiac physiology in Drosophila. Aim 2’s goals are to monitor
the effect of dietary intervention on the diurnal and long-term reprogramming of cardiac gene expression under
aging, obesogenic challenges and circadian rhythms disruption. Aim 3 will employ genetic validation of circadian
clock with other identified genes/pathways mediating the effect of eating pattern on cardiac health.
Our study will use hypothesis-driven experiments to address the molecular basis of the alarming public
health problem of age and obesity-induced cardiac dysfunction associated with circadian dysregulation.
Successful completion of this proposal will dramatically accelerate our understanding of the impact of daily
rhythms on cardiac muscle physiology. The TRF paradigm may prove applicable to human health through
application of community-based approaches to ameliorating obesity-induced comorbidities and thereby
improving cardiovascular and metabolic health.
项目概要:
遗传和生活方式对生物钟的干扰会引发心血管疾病。拟议
这项研究将探讨衰老、肥胖和昼夜节律紊乱如何与心脏代谢紊乱联系在一起,
以及时间限制进料(TRF)如何减轻这些缺陷。心血管疾病的主要危险因素
疾病是年龄、轮班工作、高能量饮食和异常的饮食/睡眠模式。这些因素中的每一
扰乱了昼夜节律,并且已经在模型生物中表明,昼夜节律的遗传扰动
生物钟增加了心脏病的发病率和严重程度。例如,一个异常的饮食模式,
在控制饮食后,人类患心血管疾病的风险增加55%
和生活方式,可能是由于生物钟的破坏。此外,生物钟基因的突变容易导致心脏病,
疾病和光诱导的昼夜节律紊乱进一步恶化了心脏异常。相反,TRF
在不减少热量摄入的情况下,已经显示出预防各种代谢紊乱和减弱
与年龄相关的心功能障碍然而,昼夜节律钟中断与心脏代谢的致病性联系,
然而,目前尚未在分子或遗传水平上评估TRF干预的潜在益处。
因此,我们的科学前提是,影响昼夜节律的因素提供了新的途径来了解
心脏代谢紊乱的病因学和衰减。
为了解决这一令人担忧的公共卫生问题的机制基础,我们开发了新的
果蝇(果蝇)模型,以减轻年龄,肥胖和昼夜节律紊乱诱导的心脏
通过使用TRF强制进食/禁食节律来治疗疾病。果蝇将作为一个很好的模型系统,
生理节律、能量代谢和心肌生理学的基本发现。拟议目标1
研究的目的是确定TRF在延缓衰老、致肥胖挑战
和昼夜节律紊乱引起的果蝇心脏生理恶化。目标2的目标是监测
饮食干预对心脏基因表达的昼夜和长期重编程的影响
衰老、肥胖挑战和昼夜节律紊乱。目标3将采用生物钟的遗传验证
时钟与其他已确定的基因/途径介导的饮食模式对心脏健康的影响。
我们的研究将使用假设驱动的实验来解决令人震惊的公众的分子基础
与昼夜节律失调相关年龄和肥胖引起的心脏功能障碍的健康问题。
成功完成这一提案将大大加快我们对日常影响的理解
对心脏肌肉生理的影响。扶轮基金会范例可能证明适用于人类健康,
应用基于社区的方法改善肥胖引起的合并症,
改善心血管和代谢健康。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Girish C. Melkani其他文献
Time-restricted feeding mediated synchronization of circadian rhythms to sustain cardiovascular health
限时进食介导生物钟节律的同步以维持心血管健康
- DOI:
10.1016/j.yjmcc.2025.07.007 - 发表时间:
2025-09-01 - 期刊:
- 影响因子:4.700
- 作者:
Girish C. Melkani - 通讯作者:
Girish C. Melkani
Linkage of circadian rhythm disruptions with Alzheimer's disease and therapeutic interventions
昼夜节律紊乱与阿尔茨海默病的关联及治疗干预
- DOI:
10.1016/j.apsb.2025.04.011 - 发表时间:
2025-06-01 - 期刊:
- 影响因子:14.600
- 作者:
Kishore Madamanchi;Jianhua Zhang;Girish C. Melkani - 通讯作者:
Girish C. Melkani
Exploration and Suppression of Cardiac Amyloidosis Induced by Huntington's Disease-Causing Amyloid in the Drosophila Heart Model
- DOI:
10.1016/j.bpj.2011.11.1923 - 发表时间:
2012-01-31 - 期刊:
- 影响因子:
- 作者:
Girish C. Melkani;Rolf Bodmer;Karen Ocorr;Sanford I. Bernstein - 通讯作者:
Sanford I. Bernstein
The E706K IBM3 Myosin Mutation Depresses the Chemomechanical Properties and Increases the Lability of the Molecular Motor
- DOI:
10.1016/j.bpj.2010.12.909 - 发表时间:
2011-02-02 - 期刊:
- 影响因子:
- 作者:
Anthony Cammarato;Yang Wang;Anju Melkani;Girish C. Melkani;Adam Bialobrodski;Jennifer A. Suggs;William A. Kronert;Sanford I. Bernstein - 通讯作者:
Sanford I. Bernstein
Kinetic Characterization of Converter and Relay Loop Domain Interaction in Drosophila Myosin Sub-Fragment 1
- DOI:
10.1016/j.bpj.2011.11.812 - 发表时间:
2012-01-31 - 期刊:
- 影响因子:
- 作者:
Marieke J. Bloemink;Girish C. Melkani;Michael A. Geeves;Sanford I. Bernstein - 通讯作者:
Sanford I. Bernstein
Girish C. Melkani的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Girish C. Melkani', 18)}}的其他基金
Promoting circadian rhythms to optimize gut-to-brain signaling for Alzheimer's disease
促进昼夜节律,优化阿尔茨海默病的肠道到大脑信号传导
- 批准号:
10717948 - 财政年份:2023
- 资助金额:
$ 39.07万 - 项目类别:
Optimized Circadian Rhythms for the Prevention of Alzheimer's Disease
优化昼夜节律以预防阿尔茨海默病
- 批准号:
10037591 - 财政年份:2020
- 资助金额:
$ 39.07万 - 项目类别:
Dissecting Causal Role of Insomnia in Cardiovascular Disease
剖析失眠与心血管疾病的因果关系
- 批准号:
10455830 - 财政年份:2020
- 资助金额:
$ 39.07万 - 项目类别:
Dissecting Causal Role of Insomnia in Cardiovascular Disease
剖析失眠与心血管疾病的因果关系
- 批准号:
9974174 - 财政年份:2020
- 资助金额:
$ 39.07万 - 项目类别:
Dissecting Causal Role of Insomnia in Cardiovascular Disease
剖析失眠与心血管疾病的因果关系
- 批准号:
10621177 - 财政年份:2020
- 资助金额:
$ 39.07万 - 项目类别:
Molecular basis of circadian rhythms disruptions linked cardiometabolic disorders and their mitigation using dietary intervention
昼夜节律紊乱的分子基础与心脏代谢紊乱及其通过饮食干预的缓解
- 批准号:
10307949 - 财政年份:2020
- 资助金额:
$ 39.07万 - 项目类别:
Molecular basis of circadian rhythms disruptions linked cardiometabolic disorders and their mitigation using dietary intervention
昼夜节律紊乱的分子基础与心脏代谢紊乱及其通过饮食干预的缓解
- 批准号:
10180848 - 财政年份:2020
- 资助金额:
$ 39.07万 - 项目类别:
Dissecting Causal Role of Insomnia in Cardiovascular Disease
剖析失眠与心血管疾病的因果关系
- 批准号:
10159305 - 财政年份:2020
- 资助金额:
$ 39.07万 - 项目类别:
Molecular basis of circadian rhythms disruptions linked cardiometabolic disorders and their mitigation using dietary intervention
昼夜节律紊乱的分子基础与心脏代谢紊乱及其通过饮食干预的缓解
- 批准号:
10656450 - 财政年份:2020
- 资助金额:
$ 39.07万 - 项目类别:
Dissecting Causal Role of Insomnia in Cardiovascular Disease
剖析失眠与心血管疾病的因果关系
- 批准号:
10399555 - 财政年份:2020
- 资助金额:
$ 39.07万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 39.07万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 39.07万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 39.07万 - 项目类别:
Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 39.07万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 39.07万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 39.07万 - 项目类别:
Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
- 批准号:
2230829 - 财政年份:2023
- 资助金额:
$ 39.07万 - 项目类别:
Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 39.07万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 39.07万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 39.07万 - 项目类别:
Grant-in-Aid for Scientific Research (C)