ENDOCANNABINOID BIOMARKERS OF OBESITY USING INTEGRATED GENOMICS AND METABOLOMICS
使用综合基因组学和代谢组学研究肥胖的内源性大麻素生物标志物
基本信息
- 批准号:7437241
- 负责人:
- 金额:$ 18.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-06-01 至 2009-10-30
- 项目状态:已结题
- 来源:
- 关键词:2-arachidonylglycerolAddictive BehaviorAddressAffectAmericanAmidesApplications GrantsAreaAutomobile DrivingBasic ScienceBehaviorBindingBiological MarkersBloodBlood CirculationBody WeightBody fatBody measure procedureCNR1 geneCandidate Disease GeneCannabinoidsCannabisCardiovascular DiseasesCentral obesityChemicalsClinicClinicalCollaborationsComplexConsentDNA DatabasesDepositionDevelopmentDiagnosticDiagnostic testsDiseaseDrug AddictionDrug abuseEatingEndocannabinoidsEnrollmentEnvironmental Risk FactorEnzymesEpidemicEquipment and supply inventoriesEthnic OriginFamily memberFatty AcidsFatty acid glycerol estersFood Intake RegulationFresh Frozen PlasmasFutureGTP-Binding ProteinsGene AbnormalityGene MutationGenesGeneticGenetic VariationGenomicsGoalsHealthHigh PrevalenceHumanIndividualIntestinesLaboratoriesLaboratory ResearchLigandsLipidsMeasuresMetabolic syndromeMethodsMissense MutationMolecularMolecular GeneticsMonoacylglycerol LipasesMutationMutation DetectionNon-Insulin-Dependent Diabetes MellitusObesityOther FindingOverweightPathway interactionsPatientsPeripheralPhasePhenotypePlasmaPlayPopulationPrevalenceProbabilityPublic HealthPublicationsPublishingRateResearchResearch PersonnelResearch Project GrantsRewardsRiskRisk AssessmentRisk FactorsRoleSamplingScreening procedureSignal TransductionSignaling MoleculeSourceStagingSystemTechniquesTestingThinkingVariantWeightWeight maintenance regimenWorkanandamidebasecardiovascular risk factorcase controlclinically relevantcravingdesignfatty acid amide hydrolasefeedinggene discoveryhuman studyimprovedlipid metabolismmetabolomicsnovelobesity treatmentresearch and developmentresearch studyresponserimonabant
项目摘要
DESCRIPTION (provided by applicant): The primary goal of this CEBRA grant is to utilize a novel integrated genomics and metabolomics approach to develop clinically relevant and readily available endocannabinoid system (ECS) biomarkers of overweight disorders that will improve risk assessment and selection of ECS-based disease modifying therapies for affected individuals. This project is directly related to public health because overweight (OW) and obesity (OB) are considered to be one of the most serious, pervasive and costly global public health problems of the twenty-first century. Although the causes, risk factors and complications are thought to involve many complex genetic and environmental factors, the endocannabinoid system has recently been identified as playing a major role in the regulation of food intake and fat metabolism and, consequently, in the development of OW and OB. The objective is to identify and validate circulating ECS biomarkers that include genetic mutations in the main endocannabinoid inactivating enzymes (FAAH and MAGL) and metabolomic profiling of fatty acid amide bioactive lipids that are elevated in the circulation of OW and OB subjects compared to case control populations. Integration of the genetic and metabolomic biomarker findings will enable the development of an ECS risk profile for use in diagnostic assessments, disease staging and likelihood of response to endocannabinoid antagonist therapies such as Rimonabant (Acomplia). This project addresses an urgent need by developing circulating endocannabinoid biomarkers that may be used from basic research to the clinic. Our working hypothesis is that subjects with genetically reduced FAAH or MAGL activity and heightened levels of endocannabinoid tone would be particularly amenable to the weight-lowering effects of Rimonabant. Since obesity disorders are thought to be a manifestation of a type of addictive behavior with abnormal reward and craving responses, the endocannabinoid biomarkers developed through this CEBRA will be directly relevant not only to the expanding obesity epidemic but may also be relevant to drug addiction behaviors. This project will significantly accelerate future obesity research and will support the development of more novel ECS-based treatment options as a result of increased clinical and investigational use of these endocannabinoid biomarkers for overweight and obesity worldwide. This cutting edge basic research project is designed to find new markers of overweight and obesity in the blood of people with these disorders. We will measure the body's own circulating Cannabis-like chemicals in patients and find gene abnormalities that are risks for overweight and obesity. Our findings will be used to improve public health by helping people with the choice of the best treatment for their obesity problems, find other family members at risk of becoming obese and by the discovery of risk factors that could produce new obesity treatments through more laboratory research.
该CEBRA资助的主要目标是利用一种新的综合基因组学和代谢组学方法来开发超重疾病的临床相关和易于获得的内源性大麻素系统(ECS)生物标志物,这将改善风险评估和选择受影响个体的基于ECS的疾病修饰疗法。该项目与公共卫生直接相关,因为超重和肥胖被认为是二十一世纪最严重、最普遍和代价最高的全球公共卫生问题之一。虽然原因,风险因素和并发症被认为涉及许多复杂的遗传和环境因素,但内源性大麻素系统最近被确定为在调节食物摄入和脂肪代谢中发挥重要作用,因此,在OW和OB的发展中发挥重要作用。目的是识别和验证循环ECS生物标志物,包括主要内源性大麻素灭活酶(FAAH和MAGL)的基因突变,以及与病例对照人群相比,OW和OB受试者循环中升高的脂肪酸酰胺生物活性脂质的代谢组学分析。遗传和代谢组学生物标志物研究结果的整合将有助于开发ECS风险特征,用于诊断评估,疾病分期和对内源性大麻素拮抗剂治疗(如利莫那班(Acomplia))的反应可能性。该项目通过开发可从基础研究到临床使用的循环内源性大麻素生物标志物来解决迫切需要。我们的工作假设是,遗传性FAAH或MAGL活性降低和内源性大麻素水平升高的受试者将特别适合利莫那班的减肥作用。由于肥胖症被认为是一种具有异常奖励和渴望反应的成瘾行为的表现,因此通过CEBRA开发的内源性大麻素生物标志物不仅与不断扩大的肥胖流行病直接相关,而且还可能与药物成瘾行为相关。该项目将大大加速未来的肥胖研究,并将支持开发更多基于ECS的新型治疗方案,因为这些内源性大麻素生物标志物在全球超重和肥胖的临床和研究中的使用增加。这项尖端的基础研究项目旨在发现患有这些疾病的人血液中超重和肥胖的新标志物。我们将测量患者体内循环的大麻样化学物质,并发现基因异常是超重和肥胖的风险。我们的研究结果将用于改善公共卫生,帮助人们选择最佳治疗肥胖问题的方法,找到其他有肥胖风险的家庭成员,并通过更多的实验室研究发现可能产生新的肥胖治疗方法的风险因素。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Biomarkers of endocannabinoid system activation in severe obesity.
- DOI:10.1371/journal.pone.0008792
- 发表时间:2010-01-20
- 期刊:
- 影响因子:3.7
- 作者:Sipe JC;Scott TM;Murray S;Harismendy O;Simon GM;Cravatt BF;Waalen J
- 通讯作者:Waalen J
Cladribine tablets: a potential new short-course annual treatment for relapsing multiple sclerosis.
克拉屈滨片剂:一种潜在的新的短期年度治疗复发性多发性硬化症的方法。
- DOI:10.1586/ern.10.12
- 发表时间:2010
- 期刊:
- 影响因子:4.3
- 作者:Sipe,JackC
- 通讯作者:Sipe,JackC
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{{ truncateString('JACK C SIPE', 18)}}的其他基金
ENDOCANNABINOID BIOMARKERS OF OBESITY USING INTEGRATED GENOMICS AND METABOLOMICS
使用综合基因组学和代谢组学研究肥胖的内源性大麻素生物标志物
- 批准号:
7294386 - 财政年份:2007
- 资助金额:
$ 18.57万 - 项目类别:
FAAH GENE MUTATIONS: RISK FACTORS IN DRUG USE/ADDICTION
FAAH 基因突变:吸毒/成瘾的风险因素
- 批准号:
6864827 - 财政年份:2004
- 资助金额:
$ 18.57万 - 项目类别:
FAAH GENE MUTATIONS: RISK FACTORS IN DRUG USE/ADDICTION
FAAH 基因突变:吸毒/成瘾的风险因素
- 批准号:
7004568 - 财政年份:2004
- 资助金额:
$ 18.57万 - 项目类别:
2-CdA for chronic progressive multiple sclerosis
2-CdA 治疗慢性进行性多发性硬化症
- 批准号:
7042965 - 财政年份:2004
- 资助金额:
$ 18.57万 - 项目类别:
FAAH GENE MUTATIONS: RISK FACTORS IN DRUG USE/ADDICTION
FAAH 基因突变:吸毒/成瘾的风险因素
- 批准号:
6772115 - 财政年份:2004
- 资助金额:
$ 18.57万 - 项目类别:
2CDA IN RELAPSING/REMITTING MULTIPLE SCLEROSIS
2CDA 在复发/缓解多发性硬化症中的作用
- 批准号:
6307349 - 财政年份:1999
- 资助金额:
$ 18.57万 - 项目类别:
2-CHLORODEOXYADENOSINE (2CDA) FOR CHRONIC PROGRESSIVE MULTIPLE SCLEROSIS
2-氯脱氧腺苷 (2CDA) 治疗慢性进行性多发性硬化症
- 批准号:
6307369 - 财政年份:1999
- 资助金额:
$ 18.57万 - 项目类别:
2-CHLORODEOXYADENOSINE (2CDA) FOR CHRONIC PROGRESSIVE MULTIPLE SCLEROSIS
2-氯脱氧腺苷 (2CDA) 治疗慢性进行性多发性硬化症
- 批准号:
6118077 - 财政年份:1998
- 资助金额:
$ 18.57万 - 项目类别:
2CDA IN RELAPSING/REMITTING MULTIPLE SCLEROSIS
2CDA 在复发/缓解多发性硬化症中的作用
- 批准号:
6118102 - 财政年份:1998
- 资助金额:
$ 18.57万 - 项目类别:
2CDA IN RELAPSING/REMITTING MULTIPLE SCLEROSIS
2CDA 在复发/缓解多发性硬化症中的作用
- 批准号:
6279297 - 财政年份:1997
- 资助金额:
$ 18.57万 - 项目类别:
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