Regulation of lipogenesis by TCA cycle metabolism
TCA 循环代谢调节脂肪生成
基本信息
- 批准号:10181447
- 负责人:
- 金额:$ 42.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-21 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:Acetyl Coenzyme AAnalytical ChemistryCarbohydratesCardiovascular DiseasesChargeCitratesCitric Acid CycleComplementConsumptionCytosolDataDiabetes MellitusDietDiseaseDyslipidemiasEquilibriumEsterificationFastingGene ExpressionGenesGenetic TranscriptionGluconeogenesisGoalsHormonesImpairmentInfectionKnockout MiceLinkLipidsLiverMalatesMalignant NeoplasmsMalonyl Coenzyme AMediatingMetabolicMetabolismMitochondriaModelingMusNADPNerve DegenerationObesityOrganismOxaloacetatesOxidation-ReductionOxidesPathologicPathway interactionsPhosphoenolpyruvate CarboxylasePhosphorylationPhysiologyPyruvatePyruvate CarboxylaseReactionRegulationRoleSourceSucroseTestingTracerTranscriptional Regulationcitrate carrierexperimental studyfeedingin vivolipid biosynthesislipid mediatorlipid metabolismloss of functionmalic enzymemetabolomicsmouse geneticsnutritionoxidized lipidprogramsresponsestable isotope
项目摘要
Project Summary:
Lipogenesis is essential for normal physiology and its dysregulation is a notable feature of obesity, diabetes,
cardiovascular disease, cancer, neurodegeneration and infection. Classical regulation of de novo
lipogenesis involves transcriptional regulation of lipogenic gene expression via hormone mediated SREBP
activation, and/or carbohydrate sensing via ChREBP activation. However, neither program facilitates
substrate handling nor set the cellular energy status amenable to lipogenic conditions. The mitochondria,
specifically the TCA cycle, is the putative source of acetyl-CoA used for lipid synthesis but before transport
to the cytosol, it is converted to citrate, a step that consumes TCA cycle intermediates. The balance
between TCA cycle cataplerosis (loss of TCA cycle intermediates) and anaplerosis (replenishment of TCA
cycle intermediates) and may help to determine the rate at which citrate can be used for lipid synthesis.
These pathways are known to be disrupted in many diseases, that also have pathological lipid metabolism.
Thus, we will examine how anaplerotic and cataplerotic pathways of the TCA cycle help to mediate the
appropriate lipogenic response to nutrition, by promoting substrate (e.g. citrate) availability and/or cellular
energy status necessary for lipogenic reactions. We will use state of the art stable isotope tracers, analytical
chemistry platforms and mouse genetics to evaluate the role of these pathways in controlling rates of lipid
synthesis. Completion of this project will identify new metabolic mechanisms for the regulation of lipid
synthesis that complement transcriptional mechanisms and may have particular relevance to the growing
list of diseases known to disrupt TCA cycle metabolism.
项目总结:
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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Shawn C Burgess其他文献
Shawn C Burgess的其他文献
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{{ truncateString('Shawn C Burgess', 18)}}的其他基金
CORE 3 - Quantitative Metabolism and Imaging Core
CORE 3 - 定量代谢和成像核心
- 批准号:
10657785 - 财政年份:2022
- 资助金额:
$ 42.75万 - 项目类别:
CORE 3 - Quantitative Metabolism and Imaging Core
CORE 3 - 定量代谢和成像核心
- 批准号:
10512735 - 财政年份:2022
- 资助金额:
$ 42.75万 - 项目类别:
Regulation of lipogenesis by TCA cycle metabolism
TCA 循环代谢调节脂肪生成
- 批准号:
10570169 - 财政年份:2021
- 资助金额:
$ 42.75万 - 项目类别:
Regulation of lipogenesis by TCA cycle metabolism
TCA 循环代谢调节脂肪生成
- 批准号:
10396106 - 财政年份:2021
- 资助金额:
$ 42.75万 - 项目类别:
Factors Controlling Metabolic Flux in the Liver by NMR Isotopomer Analysis
通过 NMR 同位素异构体分析控制肝脏代谢通量的因素
- 批准号:
8009212 - 财政年份:2010
- 资助金额:
$ 42.75万 - 项目类别:
Factors Controlling Metabolic Flux in the Liver by NMR Isotopomer Analysis
通过 NMR 同位素异构体分析控制肝脏代谢通量的因素
- 批准号:
8012817 - 财政年份:2008
- 资助金额:
$ 42.75万 - 项目类别:
Factors Controlling Metabolic Flux in the Liver by NMR Isotopomer Analysis
通过 NMR 同位素异构体分析控制肝脏代谢通量的因素
- 批准号:
8209228 - 财政年份:2008
- 资助金额:
$ 42.75万 - 项目类别:
Factors controlling metabolic flux in the liver by NMR isotopomer analysis
通过核磁共振同位素分析控制肝脏代谢通量的因素
- 批准号:
8440067 - 财政年份:2008
- 资助金额:
$ 42.75万 - 项目类别:
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