Circulating endocannabinoids in rats: Assay development and validation
大鼠循环内源性大麻素:检测方法开发和验证
基本信息
- 批准号:9306814
- 负责人:
- 金额:$ 7.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2019-06-30
- 项目状态:已结题
- 来源:
- 关键词:2-arachidonylglycerolAcuteAdipose tissueAdultAffectAmericanAmericasAnimal ModelAnimalsBehaviorBehavioralBiological AssayBloodBlood CirculationBrainCNR1 geneCaloriesCardiovascular DiseasesCessation of lifeCircadian RhythmsComorbidityConsumptionDataDaughterDetectionDiabetes MellitusDrug AddictionEatingEating DisordersEndocannabinoidsEnergy IntakeEpidemicEthanolaminesExertionExhibitsFaceFatty acid glycerol estersFoodFood EnergyFood Intake RegulationFood deprivation (experimental)FrightFutureGlucoseGlycogenHealthHigh PrevalenceHumanHyperphagiaIndividualIntakeIonsIsotopesLeadLife ExpectancyLigandsLightLipidsMalignant NeoplasmsMeasurementMeasuresMetabolicModernizationMood DisordersMuscleNutrientObesityOdorsParacrine CommunicationPatternPeripheralPhysiologicalPlasmaPlayPre-Clinical ModelProcessPsychological StressPublic HealthRattusReceptor SignalingRegulationRelapseResearch Project GrantsRewardsRoleSchemeSeriesSignaling MoleculeSiteSocietiesSourceStressSystemTestingThermogenesisTimeTissuesTranslational ResearchTranslationsUnited StatesValidationVitaminsWithdrawalacute stressassay developmentawakebrain circulationdesignemotional factorexperimental studyfallsfood consumptionfood restrictionhuman datainnovationinterestliquid chromatography mass spectrometrynutritionresponsetrend
项目摘要
The mechanisms that regulate the intake of food are vital for survival and health. While too little food
consumption can lead to death, an equal or greater problem in 21st century America is the over-consumption of
calorie-dense and inadequate consumption of vitamin-rich foods, resulting in obesity and poor nutrition. CB1
cannabinoid receptors (CB1R) in the brain play a vital role in the regulation of food intake, while activation of
CB1R in peripheral tissues results in increased fat and glycogen storage; reduced glucose utilization by
muscles; and reduced thermogenesis in brown adipose. Endocannabinoids are present in the human
circulation and their concentrations are regulated by metabolic state and exhibit a circadian pattern. These
previous findings lead us to the overall hypotheses that endocannabinoids in the circulation convey information
about the need for additional caloric intake and that sustained, high endocannabinoid concentrations contribute
to overeating. The objectives of this proposal are to establish and characterize an assay system in which
endocannabinoid concentrations in the circulation of awake, freely behaving rats are determined. We will
examine changes in endocannabinoid concentrations across the daily cycle; and following acute food
restriction and stress, as these have all been shown to impact circulating endocannabinoid concentrations in
humans. We will carry out three specific aims. The first aim is to optimize the endocannabinoid measurement
in rat plasma; determining the limits of detection and quantification, and robustness. The second aim is to
apply the assay to measure the circadian changes in circulating endocannabinoid concentrations in
relationship to other metabolic signaling molecules; and to examine the effects of a brief period of food
deprivation. The third aim will examine the time course of the effects of fear-evoking odor presentation on
circulating endocannabinoids. Successful completion of these studies will provide the basis for future studies,
including exploration of the mechanisms by which changes in energy status affect endocannabinoids in the
circulation; the tissue source of the endocannabinoids in the circulation; and, most importantly, whether the
endocannabinoids entering the brain from the circulation convey information about metabolic status to brain
reward circuit activity. These studies are highly translatable to humans because endocannabinoid
concentrations are easily measured in human blood. Indeed, the innovation of this project lies in its "beside to
bench" translation of human observations to an animal model that is amenable to mechanistic studies. The
studies in this project will increase our understanding of several processes important in the regulation of
circulating endocannabinoid concentrations and will set the stage for future human and animal studies of their
role in eating disorders, drug addiction and mood disorders.
调节食物摄入量的机制对生存和健康至关重要。虽然食物太少
消费可以导致死亡,21世纪美国面临的一个同等或更大的问题是过度消费
卡路里密集和摄入维生素丰富的食物,导致肥胖和营养不良。CB1
大脑中的大麻素受体(CB1R)在调节食物摄入量方面发挥着至关重要的作用,而激活
外周组织中的CB1R导致脂肪和糖原储存增加;通过
肌肉;棕色脂肪产热减少。内源性大麻素存在于人体内。
循环及其浓度受代谢状态的调节,呈昼夜节律。这些
以前的发现使我们得出了循环中内源性大麻素传递信息的总体假设。
关于需要额外的卡路里摄入,以及持续的高内源性大麻素浓度有助于
为了暴饮暴食。这项提案的目标是建立和描述一种检测系统,在该系统中
测定清醒、自由活动大鼠循环中的内源性大麻素浓度。我们会
检查内源性大麻素浓度在每日周期中的变化;以及以下急性食物
限制和应激,因为这些都被证明影响循环中内源性大麻素的浓度
人类。我们将落实三个具体目标。第一个目标是优化内源性大麻素的测定。
在大鼠血浆中;确定检测和定量的限度,以及稳健性。第二个目标是
应用该方法测定大鼠血液循环内大麻素浓度的昼夜变化
与其他代谢信号分子的关系;以及检查短暂的食物时期的影响
剥夺。第三个目标是研究引起恐惧的气味呈现对
循环中的内源性大麻素。这些研究的圆满完成将为今后的研究奠定基础。
包括探索能量状态变化影响体内内源性大麻素的机制。
循环;循环中内源性大麻素的组织来源;最重要的是,
从循环进入大脑的内源性大麻素将有关代谢状态的信息传递给大脑
奖励巡回活动。这些研究对人类具有高度的可译性,因为内源性大麻素
人体血液中的浓度很容易测量。确实,这个项目的创新之处在于它的
将人类的观察转化为易于进行机械学研究的动物模型。
这个项目的研究将增加我们对几个重要的过程的理解
循环内大麻素浓度,并将为未来的人类和动物研究其
在进食障碍、药物成瘾和情绪障碍中的作用。
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)
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Cecilia J Hillard其他文献
Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?
循环内源性大麻素:它们来自何处以及去向何方?
- DOI:
10.1038/npp.2017.130 - 发表时间:
2017-06-27 - 期刊:
- 影响因子:7.100
- 作者:
Cecilia J Hillard - 通讯作者:
Cecilia J Hillard
Cecilia J Hillard的其他文献
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{{ truncateString('Cecilia J Hillard', 18)}}的其他基金
2023 Cannabinoid Function in the CNS Gordon Research Conference and Gordon Research Seminar
2023中枢神经系统戈登研究会议和戈登研究研讨会大麻素功能
- 批准号:
10683605 - 财政年份:2023
- 资助金额:
$ 7.7万 - 项目类别:
Mechanisms underlying the influence of stress on drug-seeking behavior
压力对药物寻求行为影响的机制
- 批准号:
10752220 - 财政年份:2023
- 资助金额:
$ 7.7万 - 项目类别:
Examining the impact of circulating endocannabinoid levels on neurocognition, mood, and early cannabis use in youth enrolled in the ABCD Study
检查循环内源性大麻素水平对参加 ABCD 研究的青少年的神经认知、情绪和早期大麻使用的影响
- 批准号:
9916212 - 财政年份:2019
- 资助金额:
$ 7.7万 - 项目类别:
Circuit-specific actions of endocannabinoids in stress and mood disorders
内源性大麻素在压力和情绪障碍中的电路特异性作用
- 批准号:
10477473 - 财政年份:2019
- 资助金额:
$ 7.7万 - 项目类别:
Circuit-specific actions of endocannabinoids in stress and mood disorders
内源性大麻素在压力和情绪障碍中的电路特异性作用
- 批准号:
10238098 - 财政年份:2019
- 资助金额:
$ 7.7万 - 项目类别:
Circuit-specific actions of endocannabinoids in stress and mood disorders
内源性大麻素在压力和情绪障碍中的电路特异性作用
- 批准号:
10013295 - 财政年份:2019
- 资助金额:
$ 7.7万 - 项目类别:
Examining the impact of circulating endocannabinoid levels on neurocognition, mood, and early cannabis use in youth enrolled in the ABCD Study
检查循环内源性大麻素水平对参加 ABCD 研究的青少年的神经认知、情绪和早期大麻使用的影响
- 批准号:
10019508 - 财政年份:2019
- 资助金额:
$ 7.7万 - 项目类别:
Circuit-specific actions of endocannabinoids in stress and mood disorders
内源性大麻素在压力和情绪障碍中的电路特异性作用
- 批准号:
10689093 - 财政年份:2019
- 资助金额:
$ 7.7万 - 项目类别:
CB2 Cannabinoid Receptors and Cocaine Action: Studies with Conditional Knock Outs
CB2 大麻素受体和可卡因作用:条件敲除研究
- 批准号:
9250114 - 财政年份:2016
- 资助金额:
$ 7.7万 - 项目类别:
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