Neuroendocrine regulation of energy metabolism: role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the thermoregulatory cascade
能量代谢的神经内分泌调节:垂体腺苷酸环化酶激活多肽(PACAP)在温度调节级联中的作用
基本信息
- 批准号:RGPIN-2021-04040
- 负责人:
- 金额:$ 2.04万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2021
- 资助国家:加拿大
- 起止时间:2021-01-01 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Energy balance is achieved by matching the amount of energy consumed, with the amount of energy expended. In the past 25 years, knowledge of neuronal pathways regulating energy balance has advanced substantially, driven by a desire to understand the complex physiology regulating metabolism. Neuronal pathways utilize chemical messengers called hormones (or neuropeptides) that communicate within the brain, and between the brain and the peripheral organs, to regulate how much energy is consumed and expended. The specific pathways that control appetite are well characterized; however, the pathways involved in regulating energy expenditure (basal metabolic rate, thermogenesis and physical activity) are still being realized. Some well-known hormones that influence energy balance include thyroid hormones, leptin and cortisol. There are many other hormones, however, whose actions or interactions in energy balance are not yet clear - basic knowledge of which is critical to a comprehensive understanding of energy balance in animal physiology. In my lab, we study a hormone called pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP is an ancient neuropeptide found in all vertebrates. It plays a critical role in coordinating the body's response to stress, activating or inhibiting pathways to restore balance when physiological processes have been tipped out-of-balance by stressors such as danger, starvation, injury/infection or cold. My research has identified a role for PACAP in restoring energy balance in response to cold stress by regulating thermogenesis. Thermogenesis is an energy burning pathway that is turned on in response to cold exposure and overfeeding. Shivering thermogenesis occurs in skeletal muscle in response to acute cold. In long-term cold exposure, a process called adaptive thermogenesis is turned on in a specialized type of adipose tissue, brown fat. In addition to human infants and rodents, brown fat is present in all mammals, including adult humans, and plays a significant role in maintaining energy balance throughout life. This proposal aims to characterize how PACAP and its receptors regulate thermogenesis through actions in the brain, in the "fight or flight" pathways of the sympathetic nervous system (SNS) and in brown fat in response to cold stress, exploring how PACAP acts at each level of the thermoregulatory cascade (brain-SNS-brown fat) to re-balance energy metabolism in times of thermogenic stress. Knowledge generated will elucidate how PACAP initiates and modulates the physiological response to cold stress, illuminating unknown aspects thermogenic and endocrine physiology. These foundational building blocks of physiological knowledge can be applied to diverse areas of scientific study including biological studies related to changes in body temperature such as hibernation and fever, therapeutic targeting of hormone receptors and human/animal pathophysiology of energy metabolism.
能源平衡是通过将消耗的能量量与消耗的能量量相匹配来实现的。在过去的25年中,对调节能量平衡的神经元途径的了解取得了基本上的发展,这是由于了解调节代谢的复杂生理学的愿望。神经元途径利用称为激素(或神经肽)在大脑内以及大脑和外围器官之间通信的化学信使来调节消耗和消耗多少能量。控制食欲的特定途径得到了很好的特征。然而,仍在实现调节能量消耗的途径(基础代谢率,热发生和体育活动)。一些影响能量平衡的众所周知的激素包括甲状腺激素,瘦素和皮质醇。但是,还有许多其他激素,其能量平衡中的行动或互动尚不清楚 - 基本知识对于对动物生理学的能量平衡的全面理解至关重要。在我的实验室中,我们研究了一种称为垂体腺苷酸环化酶激活多肽(PACAP)的激素。 PACAP是在所有脊椎动物中发现的古老神经肽。它在协调人体对压力的反应,激活或抑制途径以恢复平衡的途径中起着至关重要的作用。我的研究已经确定了PACAP在通过调节生热作用来响应冷应激方面恢复能量平衡中的作用。 热生成是一种能量燃烧途径,以响应冷暴露和过度喂养而打开。骨骼肌响应急性冷的骨骼肌中发抖。在长期的冷暴露中,一种称为自适应热发生的过程以一种专门的脂肪组织(棕色脂肪)打开。除了人类的婴儿和啮齿动物外,包括成年人在内的所有哺乳动物中都存在棕色脂肪,并且在维持能量平衡中起着重要作用。该提案旨在表征PACAP及其受体如何通过大脑,交感神经系统的“战斗或飞行”途径(SNS)和棕色脂肪中的“战斗或飞行”途径来调节生热,以响应冷压力,探索PACAP如何在每种情况下作用在热应激时期,热调节级联级联反应的水平(脑SNS-棕色脂肪)以重新平衡能量代谢。 产生的知识将阐明PACAP如何启动并调节对冷应激的生理反应,从而阐明未知方面的热生理和内分泌生理。这些生理知识的基础基础可以应用于科学研究的不同领域,包括与体温变化有关的生物学研究,例如冬眠和发烧,激素受体的治疗靶向以及能量代谢的人类/动物病理生理学。
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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Gray, Sarah其他文献
Flow analysis techniques for spatial and temporal measurement of nutrients in aquatic systems
- DOI:
10.1071/en05059 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:4.3
- 作者:
Gray, Sarah;Hanrahan, Grady;Worsfold, Paul - 通讯作者:
Worsfold, Paul
Generational Complexities Present New Challenges for Nurse Leaders
- DOI:
10.1016/j.mnl.2019.12.008 - 发表时间:
2020-04-01 - 期刊:
- 影响因子:1.4
- 作者:
Douglas, Kathy;Gray, Sarah - 通讯作者:
Gray, Sarah
The prevalence of deranged C-reactive protein and albumin in patients with incurable cancer approaching death
- DOI:
10.1371/journal.pone.0193693 - 发表时间:
2018-03-13 - 期刊:
- 影响因子:3.7
- 作者:
Gray, Sarah;Axelsson, Bertil - 通讯作者:
Axelsson, Bertil
Femoral head ostectomy for the treatment of acetabular fracture and coxofemoral joint luxation in a Potbelly pig
- DOI:
10.1111/vsu.12604 - 发表时间:
2017-02-01 - 期刊:
- 影响因子:1.8
- 作者:
Smith, Joe S.;Chigerwe, Munashe;Gray, Sarah - 通讯作者:
Gray, Sarah
The Adult ADHD Self-Report Scale (ASRS): utility in college students with attention-deficit/hyperactivity disorder
- DOI:
10.7717/peerj.324 - 发表时间:
2014-03-25 - 期刊:
- 影响因子:2.7
- 作者:
Gray, Sarah;Woltering, Steven;Tannock, Rosemary - 通讯作者:
Tannock, Rosemary
Gray, Sarah的其他文献
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{{ truncateString('Gray, Sarah', 18)}}的其他基金
Neuroendocrine regulation of energy metabolism: role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the thermoregulatory cascade
能量代谢的神经内分泌调节:垂体腺苷酸环化酶激活多肽(PACAP)在温度调节级联中的作用
- 批准号:
RGPIN-2021-04040 - 财政年份:2022
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Endocrine regulation of thermogenesis: role of pituitary adenylate cylase-activating polypeptide (PACAP)
产热的内分泌调节:垂体腺苷酸环化酶激活多肽(PACAP)的作用
- 批准号:
RGPIN-2015-06146 - 财政年份:2019
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Endocrine regulation of thermogenesis: role of pituitary adenylate cylase-activating polypeptide (PACAP)
产热的内分泌调节:垂体腺苷酸环化酶激活多肽(PACAP)的作用
- 批准号:
RGPIN-2015-06146 - 财政年份:2018
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Endocrine regulation of thermogenesis: role of pituitary adenylate cylase-activating polypeptide (PACAP)
产热的内分泌调节:垂体腺苷酸环化酶激活多肽(PACAP)的作用
- 批准号:
RGPIN-2015-06146 - 财政年份:2017
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Endocrine regulation of thermogenesis: role of pituitary adenylate cylase-activating polypeptide (PACAP)
产热的内分泌调节:垂体腺苷酸环化酶激活多肽(PACAP)的作用
- 批准号:
RGPIN-2015-06146 - 财政年份:2016
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Endocrine regulation of thermogenesis: role of pituitary adenylate cylase-activating polypeptide (PACAP)
产热的内分泌调节:垂体腺苷酸环化酶激活多肽(PACAP)的作用
- 批准号:
RGPIN-2015-06146 - 财政年份:2015
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in energy balance
垂体腺苷酸环化酶激活多肽(PACAP)在能量平衡中的作用
- 批准号:
355956-2008 - 财政年份:2013
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in energy balance
垂体腺苷酸环化酶激活多肽(PACAP)在能量平衡中的作用
- 批准号:
355956-2008 - 财政年份:2011
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in energy balance
垂体腺苷酸环化酶激活多肽(PACAP)在能量平衡中的作用
- 批准号:
355956-2008 - 财政年份:2010
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in energy balance
垂体腺苷酸环化酶激活多肽(PACAP)在能量平衡中的作用
- 批准号:
355956-2008 - 财政年份:2009
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
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Neuroendocrine regulation of energy metabolism: role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the thermoregulatory cascade
能量代谢的神经内分泌调节:垂体腺苷酸环化酶激活多肽(PACAP)在温度调节级联中的作用
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