Neural pathways for obesity development by AgRP neurons
AgRP 神经元导致肥胖发展的神经通路
基本信息
- 批准号:10681993
- 负责人:
- 金额:$ 44.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-19 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:ART proteinAblationAcuteAddressAdultAnimal ModelAreaBacteriaBody WeightBrainChronicCuesDevelopmentDietEnergy MetabolismExhibitsFeeding behaviorsFoundationsFunctional disorderGoalsHomeostasisHypothalamic structureIndividualInvestigationKnowledgeLateral Hypothalamic AreaLeptinLeptin deficiencyMediatingMediatorModelingMusNeonatalNeural PathwaysNeuronsNeurotransmittersNutritive ValueObese MiceObesityObesity EpidemicPathway interactionsPharmaceutical PreparationsPlayPro-OpiomelanocortinRegulationResearchRodentRoleSiteSodium ChannelStructure of terminal stria nuclei of preoptic regionSubgroupThalamic structureTherapeuticViraldesigneffective therapyfeedinggamma-Aminobutyric Acidhindbrainleptin receptormidbrain central gray substancemouse geneticsmouse modelneonateneuropeptide Yneurotransmitter releaseobesity developmentoverexpressionparabrachial nucleuspharmacologicreceptor expressionsegregationside effecttherapeutic development
项目摘要
Project Summary
The development of therapeutic drugs to cure obesity has not been successful due to unwanted side effects
and limited efficacy. My long-term research goal is to delineate neural pathways responsible for body weight
homeostasis, and provide a framework for effective and specific therapeutics against obesity. Research in the
last decades has identified arcuate neurons in the hypothalamus expressing agouti-related protein (AgRP) as a
key node in feeding. Recently, we and others demonstrate that chronic activation of AgRP neurons or adult
deletion of leptin receptors in these neurons leads to massive obesity on chow diet that is comparable to leptin
deficiency. AgRP neurons are known to release GABA, NPY and AgRP and send independent and parallel
projections to several key brain sites. Importantly, the expression of leptin receptor has been suggested to be
more prominent in those AgRP neurons that project to extra-hypothalamic areas. However, how the
neurotransmitters and the individual AgRP neuron projections mediate the obesity produced by chronic
activation of AgRP neurons are unknown. Additionally, how the individual AgRP neuron projections mediates
leptin action on obesity is also unknown
To address these knowledge gaps, we aim to examine the role of AgRP individual neurotransmitters (Aim 1),
projection-specific subpopulations of AgRP neurons (Aim 2) and their LepR expression (Aim 3) in mediating
the obesity development produced by chronic AgRP neuron activation. Advanced viral tracing and
intersectional mouse genetics will be used to achieve projection-specific manipulations in AgRP neurons to
achieve robust investigation. This proposal is based on our previously established massive obese mouse
models with chronic AgRP neuron activation or LepR deletion in AgRP neurons, and utilizes a combination of
inducible deletion and tracing to ex-amine the relative importance of individual transmitters and projections in
obesity development. The results will fill the gap in the underlying neurocircuit mechanism for AgRP neurons
on obesity development and will set up stages to identify key downstream mediators and neurons mediating
leptin and AgRP neurons in obesity development, representing a significant step in understanding brain
mechanisms in body weight regulation.
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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Qingchun Tong其他文献
Qingchun Tong的其他文献
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{{ truncateString('Qingchun Tong', 18)}}的其他基金
Hypothalamic CRH Neurons in Diet-induced Obesity
下丘脑 CRH 神经元在饮食引起的肥胖中的作用
- 批准号:
10749756 - 财政年份:2023
- 资助金额:
$ 44.73万 - 项目类别:
5-HT NEURONS INTEGRATE NEURAL INPUTS TO REGULATE FOOD INTAKE
5-HT 神经元整合神经输入来调节食物摄入量
- 批准号:
10442590 - 财政年份:2020
- 资助金额:
$ 44.73万 - 项目类别:
5-HT NEURONS INTEGRATE NEURAL INPUTS TO REGULATE FOOD INTAKE
5-HT 神经元整合神经输入来调节食物摄入量
- 批准号:
10259803 - 财政年份:2020
- 资助金额:
$ 44.73万 - 项目类别:
5-HT NEURONS INTEGRATE NEURAL INPUTS TO REGULATE FOOD INTAKE
5-HT 神经元整合神经输入来调节食物摄入量
- 批准号:
10654765 - 财政年份:2020
- 资助金额:
$ 44.73万 - 项目类别:
5-HT NEURONS INTEGRATE NEURAL INPUTS TO REGULATE FOOD INTAKE
5-HT 神经元整合神经输入来调节食物摄入量
- 批准号:
10813578 - 财政年份:2020
- 资助金额:
$ 44.73万 - 项目类别:
A direct LH to PVH projection for antagonistic regulation of feeding
LH 到 PVH 的直接预测,用于拮抗调节摄食
- 批准号:
9901515 - 财政年份:2018
- 资助金额:
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Hypothalamic GABAergic Action and Energy Homeostasis
下丘脑 GABA 能作用和能量稳态
- 批准号:
8145109 - 财政年份:2010
- 资助金额:
$ 44.73万 - 项目类别:
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