Anti-obesity effects of omega 3 fatty acids in brown adipose tissue
棕色脂肪组织中欧米伽 3 脂肪酸的抗肥胖作用
基本信息
- 批准号:9171867
- 负责人:
- 金额:$ 43.46万
- 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:2016-09-01 至 2021-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdipocytesAdipose tissueAnimalsAnti-Inflammatory AgentsAnti-inflammatoryBiogenesisBiologicalBody CompositionBody WeightBody Weights and MeasuresBody fatBrown FatCardiovascular DiseasesCell Culture TechniquesCellsChronicDataDiabetes MellitusDietDietary ComponentDietary FactorsDietary InterventionEatingEicosapentaenoic AcidEnergy MetabolismEpidemicExhibitsFatty AcidsFatty acid glycerol estersFood EnergyGene ExpressionGenesGenotypeGenus HippocampusGoalsHealthHealth BenefitHealthcareHeatingHigh Fat DietHousingHumanInflammationInsulin ResistanceIntegrative MedicineInterventionKnock-outKnockout MiceLinkMediatingMesenchymal Stem CellsMetabolicMetabolic DiseasesMissionMitochondriaMolecularMorbidity - disease rateMusNutrientObesityObesity associated diseaseOmega-3 Fatty AcidsOutcomes ResearchPhysiologicalPolyunsaturated Fatty AcidsPreventionPrevention strategyPropertyProteinsPublic HealthReducing dietReportingResearchResistanceRespirationRiskRoleSafetyScienceSeriesStem cellsStrategic PlanningStressTemperatureTestingThermogenesisTissuesUnited States National Institutes of HealthUp-Regulationabstractingbasecombatdesigndietary supplementsenergy balanceevidence baseextracellularfeedingfibroblast growth factor 21glucose toleranceimprovedin vivoinnovationinstrumentinsulin sensitivityknock-downmouse modelnatural hypothermianovelnovel therapeuticsobesity preventionobesity treatmentpreventsubcutaneousuncoupling protein 1
项目摘要
Abstract/Summary
Obesity increases morbidity risks for several chronic metabolic disorders including diabetes and
cardiovascular disease, and has been linked to both systemic and white adipose tissue inflammation.
Brown adipose tissue (BAT), a fat tissue which protects against hypothermia, represents a novel target to
reduce obesity-associated metabolic disorders. The goal of this proposal is to test whether dietary
omega-3 fatty acids (namely eicosapentaenoic acid, EPA) with known anti-inflammatory effects
potentially reduce high fat associated adiposity and metabolic alterations via activation of brown fat. We
previously demonstrated that EPA-enriched high-fat diets significantly reduced diet-induced obesity,
insulin resistance, and inflammation to levels comparable to those in low-fat-fed mice. Furthermore, our
recent preliminary data show that these EPA-fed mice also manifest significantly higher brown fat
UCP1 protein levels (i.e., uncoupling protein, a BAT-specific thermogenic marker) along with significant
increases in gene expression for other markers of thermogenesis. Given the emerging role of BAT in
human studies, it is critical to understand how bioactive dietary components such as EPA activate BAT.
We hypothesize that the beneficial metabolic effects of EPA in obesity are in part mediated
through increasing BAT thermogenic capacity (via upregulation of UCP1) and induction of master
regulators of thermogenesis. This hypothesis will be tested in two specific aims through a series of
integrated cellular, molecular and physiological studies using mouse models, cultured adipocytes (white
and brown) and human mesenchymal stem cells. In aim 1 we will determine in vivo the mechanisms
mediating beneficial effects of EPA in BAT and other depots in high-fat-fed wild type and UCP1 knockout
mice. In aim 2, using white and brown adipose stem cells derived from animals in aim 1, and human
mesenchymal stem cells treated with EPA, we will further dissect the molecular mechanisms by which
EPA activates BAT and thermogenic markers (such as UCP1 and PGC1alpha). One of the major
outcomes of this research is to provide science-based evidence for potential use of omega-3 fatty acids
for improving metabolic health and possibly preventing and/or treating obesity. In addition, we will
elucidate mechanisms mediating activation of brown fat by a safe dietary intervention with other proven
health benefits. Our studies are consistent with the NIH Strategic Plan for Obesity Research and NCCIH
mission emphasizing science-based information to support the usefulness and safety of complementary
and integrative health interventions to improve health and health care. The proposed studies are highly
innovative and are expected to impact obesity treatment and prevention strategies.
摘要/摘要
肥胖增加了包括糖尿病和包括糖尿病在内的几种慢性代谢疾病的发病率风险
心血管疾病,并与全身性和白色脂肪组织炎症有关。
棕色脂肪组织(BAT)是一种预防低温的脂肪组织,代表了一个新的目标
减少与肥胖相关的代谢疾病。该建议的目的是测试饮食是否
omega-3脂肪酸(即Eicosapentaenoic,EPA)具有已知抗炎作用
通过激活棕色脂肪,可能会降低高脂肪相关的肥胖和代谢改变。我们
以前证明,富含EPA的高脂饮食可显着降低饮食引起的肥胖症,
胰岛素抵抗和与低脂喂养小鼠相当的炎症。此外,我们的
最近的初步数据表明,这些EPA喂养的小鼠也表现出明显更高的棕色脂肪
UCP1蛋白水平(即解偶联蛋白,蝙蝠特异性的热标记)以及显着
其他热生成标志物的基因表达增加。鉴于蝙蝠在
人类研究,了解生物活性饮食成分(例如EPA)如何激活蝙蝠至关重要。
我们假设EPA在肥胖症中的有益代谢作用部分是介导的
通过提高蝙蝠的热能能力(通过UCP1的上调)和诱导剂
热生成的调节剂。该假设将通过一系列特定目标进行测试
使用小鼠模型,培养的脂肪细胞(白色)综合细胞,分子和生理研究
和棕色)和人间充质干细胞。在AIM 1中,我们将在体内确定机制
在高脂喂养的野生型和UCP1敲除中,EPA在BAT和其他仓库中的有益作用
老鼠。在AIM 2中,使用AIM 1中衍生自动物的白色和棕色脂肪干细胞,人类
用EPA处理的间充质干细胞,我们将进一步剖析分子机制
EPA激活蝙蝠和热标记(例如UCP1和PGC1Alpha)。专业之一
这项研究的结果是为omega-3脂肪酸的潜在使用提供基于科学的证据
改善代谢健康,并可能预防和/或治疗肥胖症。此外,我们将
通过安全的饮食干预措施阐明介导棕色脂肪激活的机制
健康益处。我们的研究与NIH肥胖研究和NCCIH的战略计划一致
使命强调基于科学的信息,以支持互补的有用性和安全性
以及整合健康干预措施以改善健康和保健。提出的研究高度
创新,并有望影响肥胖治疗和预防策略。
项目成果
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