Setting the metabolic clock: integrating circadian and homeostatic pathways in the mediobasal hypothalamus

设置代谢时钟：整合下丘脑内侧基底节的昼夜节律和稳态通路

• 批准号: BB/L007665/1
• 负责人: Hugh Piggins
• 金额: $ 80.52万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL007665%2F1
• 关键词: Setting; metabolic; clock; integrating; circadian

Every day we must balance the internal needs of our body such as hunger and sleep with external demands such as varying availability of food, daylight etc. To cope with these varying challenges, an ancient part of our brain called the hypothalamus has evolved to contain internal 24h biological clocks that anticipate daily changes in the external world such that we are prepared for events such as sunrise and sunset. The hypothalamus has also evolved mechanisms that function like a thermostat to detect and act to correct imbalances in the body's energy and fluid levels. Unfortunately we do not know how the daily clock and homeostatic influences are combined and communicated by hypothalamic brain cells. In this proposal, we will use new technologies to monitor the electrical activity of hypothalamic brain cells and determine how daily clock and homeostatic influences are incorporated by these cells and how they respond to changes in the external world. Importantly, this research will also advance our understanding of how modern 24hr lifestyles (chronic shift work, jet lag, sleep deprivation) may be contributing to human diseases, such as metabolic syndrome.

每天我们必须平衡我们身体的内部需求，如饥饿和睡眠与外部需求，如不同的食物供应，日光等，以科普这些不同的挑战，我们大脑的一个古老的部分称为下丘脑已经进化到包含内部24小时生物钟，预测外部世界的日常变化，以便我们为日出和日落等事件做好准备。下丘脑也进化出了类似恒温器的机制，可以检测并纠正身体能量和液体水平的不平衡。不幸的是，我们不知道下丘脑脑细胞是如何将日常生物钟和体内平衡的影响结合起来并进行交流的。在这项提案中，我们将使用新技术来监测下丘脑脑细胞的电活动，并确定这些细胞如何整合日常生物钟和稳态影响，以及它们如何对外部世界的变化做出反应。重要的是，这项研究还将促进我们对现代24小时生活方式（慢性轮班工作、时差、睡眠不足）如何导致代谢综合征等人类疾病的理解。

项目成果

Feeding time.

• DOI: 10.7554/elife.08166
• 发表时间: 2015-05-27
• 期刊: eLife
• 影响因子: 7.7
• 作者: Piggins HD;Bechtold DA
• 通讯作者: Bechtold DA

Circadian regulation of mouse suprachiasmatic nuclei neuronal states shapes responses to orexin.

• DOI: 10.1111/ejn.13506
• 发表时间: 2017-03
• 期刊: The European journal of neuroscience
• 作者: Belle MD;Piggins HD
• 通讯作者: Piggins HD

Circadian clocks

• DOI: 10.1038/35011511
• 发表时间: 1999
• 期刊: Nature
• 影响因子: 64.8
• 作者: S. Abdulla

Circadian Tick-Talking Across the Neuroendocrine System and Suprachiasmatic Nuclei Circuits: The Enigmatic Communication Between the Molecular and Electrical Membrane Clocks.

• DOI: 10.1111/jne.12279
• 发表时间: 2015-07
• 期刊: Journal of neuroendocrinology
• 影响因子: 3.2
• 作者: Belle MD

PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia.

• DOI: 10.3389/fendo.2018.00632
• 发表时间: 2018
• 期刊: Frontiers in endocrinology
• 影响因子: 5.2
• 作者: Khodai T;Nunn N;Worth AA;Feetham CH;Belle MDC;Piggins HD;Luckman SM
• 通讯作者: Luckman SM