Role of Nutrient Sensing Receptors for the Gut Microbiota in Metabolism
肠道菌群营养感应受体在代谢中的作用
基本信息
- 批准号:10364023
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-01 至 2025-09-30
- 项目状态:未结题
- 来源:
- 关键词:AcetatesAffectAgonistB-LymphocytesBeta CellBiological AssayBloodButyratesCell physiologyCell secretionCellsConflict (Psychology)DataDevelopmentDiabetes MellitusDietDietary FiberDietary InterventionDiseaseDrug TargetingEventFFAR2 geneFermentationFiberGeneticHealthHormone secretionHumanIn VitroIndividualInsulin ResistanceIntakeInterventionIntestinesKnock-outKnockout MiceL CellsMeasuresMediatingMedicalMetabolicMetabolic DiseasesMetabolismModelingMorbidity - disease rateMusNon-Insulin-Dependent Diabetes MellitusNonesterified Fatty AcidsObesityOutcomeOutputPathway interactionsPeptide YYPharmaceutical PreparationsPharmacologyPhysiologyProductionPropionatesReceptor SignalingRoleSignal TransductionSiteSocietiesStructureStructure of beta Cell of isletSumSupplementationTestingTherapeuticTissuesTranslatingVeteransVolatile Fatty Acidsantagonistbody sensecell typedetection of nutrientdietaryglucagon-like peptide 1gut bacteriagut microbiomegut microbiotahuman diseasehuman tissueinsightinsulin secretionisletmeetingsmilitary veteranmortalitymouse modelnovelobesogenicreceptorreceptor functionresponsetherapeutic targettranslational potentialtranslational studywestern diet
项目摘要
ABSTRACT
Type 2 diabetes (T2D) is one of the most serious medical diseases facing our society, and
understanding the events leading to T2D, specifically the genesis of obesity and insulin
resistance, key components of T2D, is critical. Fiber, which is known to be protective against
T2D, is fermented by gut bacteria, resulting in the synthesis of short chain fatty acids (SCFAs),
predominantly acetate, propionate, and butyrate. This is one of the key proposed mechanisms
that the gut microbiome protects against these metabolic conditions. Importantly, free fatty acid
receptors 2 (FFA2) and -3 (FFA3), which sense and mediate the action of SCFAs, have altered
expression in obesity and insulin resistant states. These receptors are expressed in β cells and
in enteroendocrine (L) cells, where they are suggested to contribute to the secretion of glucagon-
like peptide-1 (GLP-1) regulating β cell function, which collectively contribute to the secretion of
insulin. These receptors, therefore, are primed to mediate the interaction between bacterial
fermentation to SCFAs and hormonal secretion. We propose to use novel genetic knockout (KO)
murine models to dissect how fiber (via SCFA production) mediates metabolic outcomes such as
obesity and insulin resistance where we will explore at the whole body (global, Aim 1) and tissue-
specific level (Aim 2), focused on the enteroinsular axis, and assess the translational component
of these receptors to human tissues (Aim 3). Overall, this study will reveal that a novel SCFA-
sensing mechanism influences host metabolic response to obesogenic challenge.
摘要
2型糖尿病是我们社会面临的最严重的医学疾病之一,
了解导致T2D的事件,特别是肥胖和胰岛素的起源
电阻是T2D的关键组件,它是至关重要的。纤维,这是已知的保护免受
T2D,由肠道细菌发酵,合成短链脂肪酸(SCFA),
主要是醋酸盐、丙酸盐和丁酸盐。这是提议的关键机制之一。
肠道微生物群对这些新陈代谢条件具有保护作用。重要的是,游离脂肪酸
感知和介导SCFAs作用的受体2(FFA2)和-3(FFA3)发生了变化
在肥胖和胰岛素抵抗状态下的表达。这些受体在β细胞中表达,并且
在肠内分泌(L)细胞中,它们被认为有助于胰高血糖素的分泌-
调节β细胞功能的类肽-1,它们共同参与分泌
胰岛素。因此,这些受体被用来调节细菌之间的相互作用。
发酵产生单链脂肪酸和激素分泌。我们建议使用新的基因敲除(KO)
小鼠模型解剖纤维(通过SCFA的产生)如何调节代谢结果,如
肥胖和胰岛素抵抗,我们将在全身(全球,目标1)和组织-
具体水平(目标2),侧重于肠岛轴线,并评估翻译部分
这些受体对人体组织的作用(目标3)。总体而言,这项研究将揭示一个新颖的SCFA-
感知机制影响宿主对肥胖挑战的代谢反应。
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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Brian Thomas Layden其他文献
Brian Thomas Layden的其他文献
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{{ truncateString('Brian Thomas Layden', 18)}}的其他基金
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10461069 - 财政年份:2020
- 资助金额:
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10513167 - 财政年份:2020
- 资助金额:
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10449719 - 财政年份:2020
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Mechanisms of diabetes from acute pancreatitis in African Americans and Hispanics
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Mechanisms of diabetes from acute pancreatitis in African Americans and Hispanics
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Role of Nutrient Sensing Receptors for the Gut Microbiota in Metabolism
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10535442 - 财政年份:2017
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10119096 - 财政年份:2015
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