Peptidergic Control of Appetitive Ingestive Behaviors
食欲摄取行为的肽能控制
基本信息
- 批准号:7775039
- 负责人:
- 金额:$ 28.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-03-15 至 2013-01-31
- 项目状态:已结题
- 来源:
- 关键词:ART proteinAffectAgonistAnimalsAppetitive BehaviorBehaviorBehavior TherapyCaloriesCardiovascular DiseasesCellsCholecystokininConsummatory BehaviorConsumptionDataDevazepideDiseaseDoseEatingEpidemicFastingFatty acid glycerol estersFeeding behaviorsFoodHamstersHealthHome environmentHumanHyperphagiaHypothalamic structureIn Situ HybridizationInjection of therapeutic agentInorganic SulfatesIntakeIntestinesLaboratoriesLaboratory RatLeptinMediator of activation proteinModelingMusNeuroanatomyNeuronsNeuropeptidesNon-Insulin-Dependent Diabetes MellitusObesityPeptide ReceptorPeptidesPeripheralPersonsPhodopus sungorusPositioning AttributeProcessResearch PersonnelRodentRoleRunningSatiationSiberian HamsterSiteStomachStrokeStructure of nucleus infundibularis hypothalamiTestingUnspecified or Sulfate Ion SulfatesWorkanorexigenic peptidebasedeprivationfeedingghrelinghrelin receptorgrowth hormone secretagogue receptorhypocretinneurochemistryneuropeptide Ynovelorexin Aparaventricular nucleuspeptide Bprogramsreceptorresearch studyresponse
项目摘要
DESCRIPTION (provided by applicant): Current approaches focusing on curtailing food intake have largely been unsuccessful in treating obesity. Because food has to be acquired (foraging, even in humans) and often is stored for later consumption (hoarding in refrigerators, freezers), this could provide another point of attack for pharmacological/behavioral intervention, but the mechanisms underlying foraging/hoarding largely are unknown. Hungry and obese humans bring home more food and higher fat/calorie food than their sated and lean counterparts, respectively. We developed a novel model of human foraging/hoarding in Siberian hamsters, where they run a prescribed number of wheel revolutions to earn food pellets and found that hungry hamsters also bring home more food, but unlike most animals, do not overeat post-fast; thus feeding is separated from foraging/hoarding making them ideal subjects. The overall purpose here is to test for the neurochemical/neuroanatomical basis of these appetitive behaviors (foraging/hoarding) across three Specific Aims (SAs). Our overarching hypothesis is that foraging/hoarding largely are governed by several orexigenic and anorexigenic peptides shown previously in laboratory rats and mice to affect feeding. We will test peripheral and central peptides that change with fasting and thus may be mechanisms underlying deprivation-induced increases in foraging/hoarding. In SA 1, we will test whether ghrelin receptor (R) antagonism blocks fasting-and ghrelin-induced increases in foraging/hoarding. We will test whether cholecystokinin (CCK), a known satiety peptide, inhibits ad libitum foraging/hoarding by giving selective CCK-R antagonists and whether systemic CCK inhibits fasting-induced increased foraging/hoarding. We will test whether the adipokine feeding suppressant leptin, inhibits fasting-induced increased foraging/hoarding. In SA 2, we will test whether selective immunolesioning of neuropeptide Y (NPY)-R bearing paraventricular nucleus (PVN) neurons via NPY-saporin blocks fasting-induced increased foraging/hoarding and which NPY- R subtype is important for fasting-induced increases by icv injections of NPY-R subtype antagonists. We will test whether icv injections of orexin A or B, peptides implicated in activity and food intake, stimulate ad libitum foraging/hoarding and whether antagonism of each receptor subtype blocks fasting-induced increased foraging/hoarding. In SA 3, we will test whether co-injection of NPY and agouti-related protein that co-localize in arcuate neurons, increase with fasting and each stimulates foraging/hoarding, will do so when co-injected at subthreshold doses. Because arcuate NPY/AgRP ghrelin-R bearing neurons likely underlie ghrelin-induced increased food intake, we will test whether blockade of downstream NPY-Rs by icv injections of subtype antagonists block ghrelin-induced increased foraging/hoarding. We will test whether destruction of downstream NPY-Rs by PVN injection of NPY-saporin blocks ghrelin-induced increased foraging/hoarding.
描述(由申请人提供):当前侧重于减少食物摄入的方法在治疗肥胖方面基本上不成功。由于食物必须被获取(觅食,即使是人类)并且通常被储存以供以后消费(囤积在冰箱、冰柜中),这可能为药理学/行为干预提供另一个攻击点,但觅食/囤积的机制很大程度上是未知。饥饿和肥胖的人分别比饱足和瘦的人带回家更多的食物和更高脂肪/热量的食物。我们在西伯利亚仓鼠中开发了一种人类觅食/囤积的新模型,它们运行规定数量的轮子旋转以获得食物颗粒,并发现饥饿的仓鼠也会带回家更多的食物,但与大多数动物不同的是,它们不会在禁食后吃得过多;因此,进食与觅食/囤积是分开的,这使它们成为理想的对象。这里的总体目的是测试三个特定目标(SA)中这些食欲行为(觅食/囤积)的神经化学/神经解剖学基础。我们的总体假设是,觅食/囤积很大程度上受到先前在实验室大鼠和小鼠中显示的几种促食欲和厌食肽的控制,这些肽会影响进食。我们将测试随禁食而变化的外周和中枢肽,因此可能是剥夺引起的觅食/囤积增加的潜在机制。在 SA 1 中,我们将测试 ghrelin 受体 (R) 拮抗作用是否会阻止禁食和 ghrelin 诱导的觅食/囤积增加。我们将测试胆囊收缩素 (CCK)(一种已知的饱腹感肽)是否通过给予选择性 CCK-R 拮抗剂来抑制随意觅食/囤积,以及全身性 CCK 是否抑制禁食引起的觅食/囤积增加。我们将测试脂肪因子摄食抑制剂瘦素是否抑制禁食引起的觅食/囤积增加。在 SA 2 中,我们将测试通过 NPY-皂草素对带有室旁核 (PVN) 神经元的神经肽 Y (NPY)-R 进行选择性免疫损伤是否会阻止禁食诱导的觅食/囤积增加,以及哪种 NPY-R 亚型对于禁食诱导的增加很重要通过ICV注射NPY-R亚型拮抗剂。我们将测试静脉注射食欲素 A 或 B(与活动和食物摄入有关的肽)是否会刺激随意觅食/囤积,以及每种受体亚型的拮抗作用是否会阻止禁食引起的觅食/囤积增加。在 SA 3 中,我们将测试共同注射 NPY 和刺鼠相关蛋白,它们共定位于弓形神经元中,随着禁食而增加,并且每种蛋白都会刺激觅食/囤积,当以阈下剂量共同注射时是否会这样做。由于弓形 NPY/AgRP ghrelin-R 神经元可能是 ghrelin 诱导的食物摄入增加的基础,因此我们将测试通过 icv 注射亚型拮抗剂对下游 NPY-R 的阻断是否会阻止 ghrelin 诱导的觅食/囤积增加。我们将测试 PVN 注射 NPY-皂草素对下游 NPY-R 的破坏是否会阻止生长素释放肽诱导的觅食/囤积增加。
项目成果
期刊论文数量(0)
专著数量(0)
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Timothy Jon Bartness其他文献
Timothy Jon Bartness的其他文献
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{{ truncateString('Timothy Jon Bartness', 18)}}的其他基金
Peptidergic Control of Appetitive Ingestive Behaviors
食欲摄取行为的肽能控制
- 批准号:
8444178 - 财政年份:2007
- 资助金额:
$ 28.74万 - 项目类别:
Peptidergic Control of Appetitive Ingestive Behaviors
食欲摄取行为的肽能控制
- 批准号:
7251031 - 财政年份:2007
- 资助金额:
$ 28.74万 - 项目类别:
Peptidergic Control of Appetitive Ingestive Behaviors
食欲摄取行为的肽能控制
- 批准号:
7567468 - 财政年份:2007
- 资助金额:
$ 28.74万 - 项目类别:
CNS MELATONIN TARGET SITES--CONTROL OF SEASONAL CYCLES
中枢神经系统褪黑激素的靶位点——季节周期的控制
- 批准号:
2248154 - 财政年份:1993
- 资助金额:
$ 28.74万 - 项目类别:
CNS MELATONIN TARGET SITES--CONTROL OF SEASONAL CYCLES
中枢神经系统褪黑激素的靶位点——季节周期的控制
- 批准号:
3387985 - 财政年份:1993
- 资助金额:
$ 28.74万 - 项目类别:
CNS MELATONIN TARGET SITES--CONTROL OF SEASONAL CYCLES
中枢神经系统褪黑激素的靶位点——季节周期的控制
- 批准号:
2248153 - 财政年份:1993
- 资助金额:
$ 28.74万 - 项目类别:
CNS MELATONIN TARGETS AND PHOTOPERIOD-INDUCED OBESITY
中枢神经系统褪黑激素目标和光周期诱发的肥胖
- 批准号:
6185258 - 财政年份:1990
- 资助金额:
$ 28.74万 - 项目类别:
CNS MELATONIN TARGETS AND PHOTOPERIOD-INDUCED OBESITY
中枢神经系统褪黑激素目标和光周期诱发的肥胖
- 批准号:
3070210 - 财政年份:1990
- 资助金额:
$ 28.74万 - 项目类别:
CNS MELATONIN TARGETS AND PHOTOPERIOD-INDUCED OBESITY
中枢神经系统褪黑激素目标和光周期诱发的肥胖
- 批准号:
2240040 - 财政年份:1990
- 资助金额:
$ 28.74万 - 项目类别:
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