VMH SF1 neurons-originated sympathetic circuits modulating iWAT and iBAT
VMH SF1 神经元起源的交感神经回路调节 iWAT 和 iBAT
基本信息
- 批准号:10635521
- 负责人:
- 金额:$ 45.33万
- 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:2023-04-17 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:AMPA ReceptorsAcclimatizationAction PotentialsAcuteAdipose tissueBrainBrown FatCentral Nervous SystemCytoplasmDataDevelopmentElectrophysiology (science)Energy MetabolismExpenditureGene ExpressionGenerationsGenesGeneticGenetic TranscriptionGlucoseGlutamate ReceptorHeadHigh Fat DietHypothalamic structureInsulinLabelLeptinLipolysisLiteratureLogicMapsMediatingMessenger RNAMetabolicMethodsMolecularMusNeuronsNeurosciencesNeurotransmitter ReceptorNorepinephrineObesityPathologicPathway interactionsPeripheralPermeabilityPhosphorylationPhotometryPhysiologicalPlayPopulationProbabilityReceptor SignalingRegulationResearch Project GrantsRoleSF1SeriesSignal TransductionSiteSliceSynapsesTNF geneTNFRSF1A geneTechniquesTemperatureTestingThalamic structureTherapeutic InterventionThermogenesisTimeTissuesTransgenic MiceTumor Necrosis Factor ReceptorWeight Gainadeno-associated viral vectorblood glucose regulationcell typecombatcomorbiditydiet-induced obesityenergy balanceenhancing factorexcitotoxicityexperimental studyfactor Afeedingglucose toleranceinflammatory markerinnovationknock-downmidbrain central gray substancemind controlneural circuitneurotransmitter releasenovelobesity developmentobesity preventionpreventreceptorreceptor expressionsatiety centersingle-cell RNA sequencingsterol esterasetransmission processtreatment strategy
项目摘要
Summary
To combat obesity and its related metabolic comorbidities, it is necessary and significant in precisely modulating
adipose tissue functions (i.e. lipolysis, beiging, thermogenesis) which play a crucial role in the control of energy
balance and glucose homeostasis. The ventromedial hypothalamus (VMH) is a well-known satiety center in the
brain to prevent body weight gain. However, the exact mechanisms and precise circuitry through which the VMH
modulates adipose tissue sympathetic outflow and function remain incompletely understood. Literature and our
recent study show that selective stimulation of neurons expressing steroidogenic factor-1 (SF1) in VMH rapidly
increases energy expenditure and heat generation. We also find that selective stimulation of VMH SF1 neuron
projections to paraventricular thalamus (PVT) elicits minimal effects on expenditure and head generation. Our
preliminary data show that selective stimulation of VMH SF1 neuron projections to PVT increases norepinephrine
(NE) contents and the phosphorylation of lipolytic hormone-sensitive lipase (p-HSL) in the inguinal white adipose
tissue (iWAT), and stimulation of SF1 neuron projections to rostral periaqueductal gray (rPAG) increases NE
contents and temperature in the inguinal brown adipose tissue (iBAT). Our results also show that cold exposure
excites a subset of VMH SF1 neurons, revealing cold-sensitive and cold-insensitive VMH SF1 neurons. We thus
hypothesize that there are molecularly distinct subsets of VMH SF1 neurons which respectively modulate iWAT
and iBAT functions through different sympathetic circuits. We focus to study VMH SF1 neurons, PVT, rPAG,
iWAT, and iBAT. We propose to identify and characterize SF1 subpopulations and sympathetic circuits that
modulate iWAT or iBAT (Aim 1), to determine the impact of cold on VMH SF1 neurons and synapse transmission
(Aim 2), and to determine if attenuating Ca2+-permeable AMPA receptor (CP-AMPAR) and tumor necrosis factor
a (TNFa) receptor (TNFR) signal in SF1 neurons can prevent obesity in HFD-fed mice (Aim 3). Overall, our
previous studies and preliminary results have enabled us to identify and characterize SF1 neuron-originated
sympathetic circuits that modulate iWAT or iBAT functions in physiological and pathological conditions. With
innovative combined neuroscience and genetic and metabolic methods and techniques such as central and
peripheral tissue photometry, electrophysiology, cell-type selective genetic, and several transgenic mouse lines,
this research project will test several novel concepts, including previously unknown VMH SF1 subpopulations
respectively modulating iWAT and iBAT functions and differentially responding to cold, cell-type specific gene
expressions, and the roles of CP-AMPAR and TNFa signals in the VMH SF1 neurons in DIO development and
prevention. The information to be collected from a series of logical studies will provide a molecular and circuit
framework that will then allow further studies by us and other groups to further understand the mechanisms for
CNS regulations of adipose tissue function and energy metabolism as well as glucose homeostasis.
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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Yunlei Yang其他文献
Yunlei Yang的其他文献
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{{ truncateString('Yunlei Yang', 18)}}的其他基金
Deciphering Neural Circuits Underlying Hippocampal Suppression of Food Intake
破译海马抑制食物摄入的神经回路
- 批准号:
9899824 - 财政年份:2016
- 资助金额:
$ 45.33万 - 项目类别:
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