Physiology and Pharmacology of BRS-3 (Bombesin Receptor Subtype-3)
BRS-3(铃蟾肽受体亚型 3)的生理学和药理学
基本信息
- 批准号:8939702
- 负责人:
- 金额:$ 31.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AblationAdrenergic AgentsAffectAffinityAgonistAreaBeta CellBlood PressureBody TemperatureBody WeightBombesinBombesin ReceptorBrainBrain StemBrown FatCannabinoidsCardiovascular DiseasesCell LineCell NucleusCellsCholelithiasisCommunicationComorbidityDataDefectDegenerative polyarthritisDrug KineticsDyslipidemiasEatingEffectivenessEnvironmentFastingG-Protein-Coupled ReceptorsGeneticGlucoseGoalsHealthHomeostasisHypertensionHypothalamic structureInfusion proceduresIslets of LangerhansKnock-in MouseKnockout MiceLeptinLife ExpectancyLigandsLightMalignant NeoplasmsMetabolicMidbrain structureMusNamesNon-Insulin-Dependent Diabetes MellitusObesityPharmacologyPhasePhenotypePhysical activityPhysiologic ThermoregulationPhysiologyPublishingRegulationReproductive BehaviorResearchRiskRodentRoleSignal PathwaySignal TransductionSiteTemperatureTissuesacute stressadrenergicattenuationbombesin receptor subtype 3complement pathwayimprovedinsulin secretioninterestmemberneuropeptide Yobesity treatmentrecombinaseresponsetool
项目摘要
Progress in FY2014 includes the following:
In order to study the specific cells, sites, tissues, and transmitters by which BRS-3 acts, we have generated floxed Brs3 mouse. This is a hugely important tool, making possible studies with conditional deletion. We also have a knock in mouse with Cre recombinase driven by Brs3, although we do not know if the Cre expression is high enough for the mouse to be useful.
We published that the reduced body temperature is more readily detected if body temperature is analyzed as a function of physical activity level and light/dark phase. Physical activity level correlated best with body temperature 4 minutes later. The Brs3 null metabolic phenotype is not due to intrinsically impaired brown adipose tissue function or in the communication of sympathetic signals from the brain to brown adipose tissue, since Brs3 null mice have intact thermogenic responses to stress, acute cold exposure, and beta3-adrenergic activation, and Brs3 null mice prefer a cooler environment. Treatment with the BRS-3 agonist MK-5046 increased brown adipose tissue temperature and body temperature in wild-type but not Brs3 null mice. Intrahypothalamic infusion of MK-5046 increased body temperature. These data indicate that BRS-3 regulation of body temperature is via a central mechanism, upstream of sympathetic efferents. The reduced body temperature in Brs3 null mice is due to altered regulation of energy homeostasis affecting higher center regulation of body temperature, rather than an intrinsic defect in brown adipose tissue.
二零一四财政年度的进展包括以下各项:
为了研究BRS-3作用的特定细胞、位点、组织和递质,我们产生了floxed Brs 3小鼠。 这是一个非常重要的工具,使条件删除研究成为可能。 我们也有一个敲入小鼠与Cre重组酶驱动的Brs 3,虽然我们不知道如果Cre表达是足够高的小鼠是有用的。
我们发表了如果将体温作为身体活动水平和亮/暗相的函数进行分析,则更容易检测到体温降低。 体力活动水平与4分钟后的体温相关性最好。Brs 3无效代谢表型不是由于内在受损的棕色脂肪组织功能或从大脑到棕色脂肪组织的交感神经信号的通信,因为Brs 3无效小鼠对应激、急性冷暴露和β 3-肾上腺素能激活具有完整的产热反应,并且Brs 3无效小鼠更喜欢较冷的环境。 用BRS-3激动剂MK-5046处理增加了野生型但不是Brs 3缺失小鼠的棕色脂肪组织温度和体温。下丘脑内输注MK-5046使体温升高。这些数据表明BRS-3对体温的调节是通过交感传出神经上游的中枢机制。Brs 3基因敲除小鼠的体温降低是由于能量稳态调节的改变影响了体温的更高中心调节,而不是棕色脂肪组织的内在缺陷。
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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MARC L REITMAN其他文献
MARC L REITMAN的其他文献
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{{ truncateString('MARC L REITMAN', 18)}}的其他基金
REGULATION OF GENE EXPRESSION RELEVANT TO THE ADIPOSE CELL AND OBESITY
脂肪细胞与肥胖相关基因表达的调控
- 批准号:
6105566 - 财政年份:
- 资助金额:
$ 31.8万 - 项目类别:
Studies in Youths & Young Adults with Obesity & T2DM (07-DK-0115, 10-DK-0163)
青少年研究
- 批准号:
8349793 - 财政年份:
- 资助金额:
$ 31.8万 - 项目类别:
Physiology and Pharmacology of BRS-3 (Bombesin Receptor Subtype-3)
BRS-3(铃蟾肽受体亚型 3)的生理学和药理学
- 批准号:
8553647 - 财政年份:
- 资助金额:
$ 31.8万 - 项目类别:
What can body temperature tell us about energy homeostasis?
体温可以告诉我们关于能量稳态的什么信息?
- 批准号:
10697821 - 财政年份:
- 资助金额:
$ 31.8万 - 项目类别:
What can body temperature tell us about energy homeostasis?
体温可以告诉我们关于能量稳态的什么信息?
- 批准号:
10248173 - 财政年份:
- 资助金额:
$ 31.8万 - 项目类别:
Physiology and Pharmacology of BRS3 (Bombesin-Like Receptor 3)
BRS3(铃蟾肽样受体 3)的生理学和药理学
- 批准号:
10001930 - 财政年份:
- 资助金额:
$ 31.8万 - 项目类别:
Role of brown adipose tissue (BAT) in energy balance
棕色脂肪组织(BAT)在能量平衡中的作用
- 批准号:
10919489 - 财政年份:
- 资助金额:
$ 31.8万 - 项目类别:
Physiology and Pharmacology of BRS-3 (Bombesin-Like Receptor 3)
BRS-3(铃蟾肽样受体 3)的生理学和药理学
- 批准号:
9356205 - 财政年份:
- 资助金额:
$ 31.8万 - 项目类别:
REGULATION OF GENE EXPRESSION RELEVANT TO THE ADIPOSE CELL AND OBESITY
脂肪细胞与肥胖相关基因表达的调控
- 批准号:
6289802 - 财政年份:
- 资助金额:
$ 31.8万 - 项目类别:
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