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Hypothalmic Circuits Regulating Energy Balance and Obesity: Synaptic Physiology

调节能量平衡和肥胖的下丘脑回路：突触生理学

基本信息

批准号：
10651471
负责人：
SHANE T HENTGES
金额：
$ 31.2万
依托单位：
WASHINGTON STATE UNIVERSITY
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：
2022-06-22 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10651471
关键词：
Hypothalmic Circuits Regulating Energy Balance

项目摘要

Project Summary According to the CDC more that 35% of U.S. adults and 20% of U.S. children are obese and therefore are at risk of life-threatening diseases including diabetes, stroke, heart disease and cancers. Further, obesity has huge economic consequences in medical care and lost wages. Studies on obesity clearly indicate important roles for hypothalamic POMC neurons in regulating aspects of energy homeostasis. These neurons have been traditionally considered to respond to post-prandial cues and maintain energy balance over protracted timescales. However, recent work from our lab and others indicate that these neurons release many transmitters and can respond and act more quickly than previously appreciated. The overall goals of this proposal are to determine how food intake and activation of these neurons changes the short-term response to food intake and alters food intake at the next meal. Specifically, we aim to learn how eating patterns might play into energy balance regulation as this is something people could readily optimize with the appropriate knowledge. We will determine the frequency with which POMC neurons can be stimulated to best reduce food intake and will determine how the activity of POMC neurons is regulated in a meal-to-meal fashion. Since POMC neuron activation usually leads to the reduction of food intake or termination of a meal, we will examine the timing between meals that yields the smallest meal size for a subsequent meal. Ultimately, the studies stand to provide mechanistic insight into the reported efficacy of intermittent fasting and may provide insight into the most beneficial timing of meals for weight loss.

项目概要根据 CDC 的数据，超过 35% 的美国成年人和 20% 的美国儿童患有肥胖症，因此处于肥胖状态患糖尿病、中风、心脏病和癌症等危及生命的疾病的风险。此外，肥胖还医疗保健和工资损失造成巨大的经济后果。关于肥胖的研究清楚地表明重要下丘脑 POMC 神经元在能量稳态调节方面的作用。这些神经元已被传统上被认为是对餐后信号做出反应并长期维持能量平衡时间尺度。然而，我们实验室和其他实验室最近的工作表明，这些神经元释放了许多发射器，并且可以比以前想象的更快地响应和采取行动。本次活动的总体目标建议确定食物摄入和这些神经元的激活如何改变短期反应食物摄入量并改变下一餐的食物摄入量。具体来说，我们的目标是了解饮食模式如何发挥作用进入能量平衡调节，因为这是人们可以通过适当的方法轻松优化的东西知识。我们将确定刺激 POMC 神经元的频率，以最好地减少食物摄入量并将决定 POMC 神经元的活动如何以膳食方式调节。自从 POMC 神经元激活通常会导致食物摄入量减少或进餐终止，我们将检查两餐之间的时间间隔，为下一餐提供最小的膳食量。最终，研究可以为间歇性禁食的报告功效提供机制上的见解，并可能提供见解进入对减肥最有利的进餐时间。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Various transgenic mouse lines to study proopiomelanocortin cells in the brain stem label disparate populations of GABAergic and glutamatergic neurons.

研究脑干中阿黑皮素原细胞的各种转基因小鼠品系标记了不同的 GABA 能和谷氨酸能神经元群体。

DOI：
10.1152/ajpregu.00047.2018
发表时间：
2018
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Rau,AndrewR;Hughes,AlexanderR;Hentges,ShaneT
通讯作者：
Hentges,ShaneT

Direct inhibition of hypothalamic proopiomelanocortin neurons by dynorphin A is mediated by the μ-opioid receptor.

强啡肽 A 对下丘脑原阿片黑皮素神经元的直接抑制是由 μ-阿片受体介导的。

DOI：
10.1113/jphysiol.2014.275339
发表时间：
2014
期刊：
The Journal of physiology
影响因子：
0
作者：
Pennock,ReaganL;Hentges,ShaneT
通讯作者：
Hentges,ShaneT

Differential expression and sensitivity of presynaptic and postsynaptic opioid receptors regulating hypothalamic proopiomelanocortin neurons.

DOI：
10.1523/jneurosci.4654-10.2011
发表时间：
2011-01-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Pennock RL;Hentges ST
通讯作者：
Hentges ST

Expression of GABAergic and glutamatergic phenotypic markers in hypothalamic proopiomelanocortin neurons.

DOI：
10.1002/cne.23127
发表时间：
2012-12-01
期刊：
JOURNAL OF COMPARATIVE NEUROLOGY
影响因子：
2.5
作者：
Jarvie, Brooke C.;Hentges, Shane T.
通讯作者：
Hentges, Shane T.

Multiple inhibitory G-protein-coupled receptors resist acute desensitization in the presynaptic but not postsynaptic compartments of neurons.

DOI：
10.1523/jneurosci.1227-12.2012
发表时间：
2012-07-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Pennock RL;Dicken MS;Hentges ST
通讯作者：
Hentges ST