The role of ventromedial hypothalamic steroidogenic factor-1 neurons in exercise-related metabolism
下丘脑腹内侧类固醇生成因子1神经元在运动相关代谢中的作用
基本信息
- 批准号:10576275
- 负责人:
- 金额:$ 3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-01 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAmericanCalciumCell NucleusCellsCentral Nervous SystemChemosensitizationChronicClassificationDataDevelopmentDiseaseExerciseFiberFoodFutureGlucose tolerance testGoalsHomeostasisHypothalamic structureImageImpairmentIndividualInstitutionInsulin ReceptorInternationalLaboratoriesMediatingMentorsMetabolicMetabolismMonitorMusNeuronsNeurosciencesNon-Insulin-Dependent Diabetes MellitusObesityPatternPennsylvaniaPerformancePhotometryPhysiologicalPlayPopulationPrevalencePublishingRegimenRegulationResearchResourcesRoleRunningSF1ScientistSensory ReceptorsSignal TransductionSkeletal MuscleSystemTechniquesTemperatureTestingTrainingTwin Multiple BirthUniversitiesWorkWritingblood glucose regulationcareerendurance exerciseenergy balanceexercise capacityexercise trainingexperienceexperimental studyfood consumptionglucose metabolismglucose toleranceimprovedin vivoindividual responseinsightleptin receptormimeticsneuralneural circuitneuromechanismneurophysiologyoptogeneticsreceptor expressionrecruitrespiratoryresponsesedentarysedentary lifestyleskillssymposiumtranscription factortreadmill
项目摘要
PROJECT SUMMARY
Nearly half of the American population is classified as obese and just under one in ten suffer from type 2 diabetes
mellitus (T2DM). Exercise protects against a number of deleterious metabolic changes that correspond with
obesity and T2DM, including impaired glucose metabolism and altered energy balance. The ventromedial
nucleus of the hypothalamus (VMH) is critical for the regulation of whole-body metabolism. Co-sponsor Dr. Joel
Elmquist has shown that the expression of the transcription factor steroidogenic factor-1 (SF1) in the dorsomedial
VMH (VMHdm) is required for normal energy homeostasis in response to metabolic challenges including
exercise. While preliminary work in sponsor Dr. J. Nicholas Betley’s laboratory has shown that the activity of
VMHdm SF1 neurons substantially increases following exercise, it remains unknown how SF1 neural activity
may mediate the metabolic effects of exercise. The main goals of the proposed research are to characterize the
neurophysiology of VMHdm SF1 neurons and their two major subtypes—those that express the leptin and insulin
receptors (LEPR and INSR)—during exercise training; and to determine the role of SF1, LEPR, and INSR neural
activity in exercise-driven changes in energy balance and glucose homeostasis. Specific Aim I experiments will
use fiber photometry and endoscopic calcium imaging to monitor the neural activity of VMHdm SF1, LEPR, and
INSR neurons during and immediately following both acute exercise and chronic exercise training. Specific Aim
II experiments will combine optogenetic manipulation of VMHdm SF1, LEPR, and INSR neurons in in exercising
and sedentary mice with metabolic chamber monitoring and glucose tolerance tests to test the necessity and
sufficiency of these neural populations to drive exercise-related changes in energy balance and glucose
homeostasis. Collectively, these experiments will open avenues for future research into the specific mechanisms
by which VMHdm neural activity contributes to the whole-body homeostatic response to metabolic challenges
such as exercise. The training plan included in this application builds upon the applicant, Dr. Ryan Post’s prior
expertise in systems neuroscience, optogenetics, and fiber photometry as he develops his skills in endoscopic
calcium imaging and metabolic techniques, and enters the field of metabolism. The application’s sponsor, Dr. J.
Nicholas Betley, and co-sponsors, Drs. Joel Elmquist and Junhyong Kim, will be instrumental in Ryan’s
completion of the proposed research and training plan. Given Dr. Betley’s expertise in the contribution of the
central nervous system to metabolism, Dr. Elmquist’s experience as a leader in the field of hypothalamic research
and metabolism, and Dr. Kim’s standing as a pre-eminent cell biologist and successful mentor, they will serve
as invaluable resources to Ryan in his development as an independent scientist. Drs. Betley, Elmquist, and Kim
will also oversee Ryan’s professional development as he attends international conferences in neuroscience and
metabolism. The training and research proposed in this application will take place at the University of
Pennsylvania, a world-class institution with a number of resources that will augment Dr. Post’s development.
项目总结
近一半的美国人被归类为肥胖,不到十分之一的人患有2型糖尿病。
糖尿病(T2 DM)。锻炼可以预防一系列有害的代谢变化,这些变化与
肥胖和2型糖尿病,包括糖代谢受损和能量平衡改变。腹内侧
下丘脑核(VMH)对全身代谢的调节起着至关重要的作用。共同赞助人乔尔博士
Elmquist已经证明转录因子类固醇生成因子-1(SF1)在背内侧的表达
VMH(VMHdm)是正常能量平衡所必需的,以应对代谢挑战,包括
锻炼身体。虽然赞助商J.Nicholas Betley博士的实验室的初步工作表明,
VMHdm SF1神经元在运动后显著增加,目前尚不清楚SF1神经活动如何
可能会调节运动的代谢效应。拟议研究的主要目标是描述
VMHdm SF1神经元及其表达瘦素和胰岛素的两种主要亚型的神经生理学
受体(LEPR和INSR)--在运动训练中;并确定SF1、LEPR和INSR神经的作用
运动中运动引起的能量平衡和葡萄糖稳态的变化。具体目标I实验将
使用纤维光度法和内窥镜钙成像来监测VMHdm SF1、LEPR和
在急性运动和慢性运动训练期间和之后的INSR神经元。特定目标
II实验将结合运动中VMHdm SF1、LEPR和INSR神经元的光遗传操作
并对久坐不动的小鼠进行代谢室监测和糖耐量试验,以测试其必要性和
这些神经细胞群体是否足以驱动运动相关的能量平衡和血糖变化
动态平衡。总的来说,这些实验将为未来对具体机制的研究开辟道路
VMHdm神经活动对代谢挑战的全身动态平衡反应的影响
比如锻炼。此申请中包含的培训计划建立在申请者Ryan Post博士之前的基础上
在系统神经科学、光遗传学和纤维光度学方面的专业知识,因为他在内窥镜方面发展了自己的技能
钙成像和代谢技术,并进入代谢领域。该应用程序的发起人J。
Nicholas Betley以及共同赞助商Joel Elmquist博士和Junhyong Kim将在Ryan的
完成拟议的研究和培训计划。鉴于贝特利博士在
中枢神经系统到新陈代谢,Elmquist博士作为下丘脑研究领域的领导者的经验
以及金博士作为一位杰出的细胞生物学家和成功的导师的地位,他们将为
对于瑞安作为一名独立科学家的发展来说,这是无价的资源。Betley博士、Elmquist博士和Kim博士
还将监督瑞安的职业发展,因为他参加了神经科学和
新陈代谢。本申请书中建议的培训和研究将在华盛顿大学进行
宾夕法尼亚州,一个世界级的机构,拥有大量的资源,将加强波斯特博士的发展。
项目成果
期刊论文数量(0)
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Ryan James Post其他文献
Ryan James Post的其他文献
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{{ truncateString('Ryan James Post', 18)}}的其他基金
The role of ventromedial hypothalamic steroidogenic factor-1 neurons in exercise-related metabolism
下丘脑腹内侧类固醇生成因子1神经元在运动相关代谢中的作用
- 批准号:
10463197 - 财政年份:2022
- 资助金额:
$ 3万 - 项目类别:
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