Regulation of Energy Balance and Intestinal Function in Ancient Fishes

古代鱼类能量平衡和肠道功能的调节

• 批准号: RGPIN-2020-05328
• 负责人: Anderson, W
• 金额: $ 4.01万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744693
• 关键词: Regulation; Energy; Balance; Intestinal; Function

Appropriate regulation of energy balance is of fundamental importance to all life on earth and is in part achieved in multi-cellular organisms by a suite of hormones released into the circulatory system that act to control uptake of nutrients across the intestine followed by, distribution, storage or use by the organism. Regulation of blood glucose in humans by insulin released from pancreatic B cells is perhaps the most intensively studied example of this. In the ancient fishes how hormones regulate uptake, storage and/or use of nutrients is largely unexplored. As `living fossils' elasmobranchs (sharks, skates and rays) and sturgeons are excellent models to address the long-term goal of my research program that is, to understand how the function of hormones like insulin and corticosteroids have evolved in vertebrates. There are three primary areas of research with short term objectives aiming to understand: 1) control of hormone release; 2) hormonal regulation of nutrient uptake across the gut; and 3) hormonal control of nutrient processing by the liver. The primary nutrient of interest is glucose; however, metabolic organization in sturgeons and in particular, elasmobranchs, indicate ketones also play an important role in whole animal energy balance. Proposed objectives focus on the regulation of insulin release in the pancreatic islet cells of both elasmobranchs and sturgeon and how glucoregulating hormones such as insulin, glucagon and GLP 1 influence uptake of glucose across the gut in these ancient fishes. The action of cortisol in sturgeon and the elasmobranch specific corticosteroid, 1alpha-hydroxycorticosterone (1 alpha-OHB), on processing of glucose and ketones in the liver in both groups of fishes will further our understanding in the mechanistic underpinnings of the stress response in these fishes. Elasmobranch specific research will examine the role the intestine microbial community plays in whole body nitrogen balance and test the novel hypothesis that through a mutualistic relationship tissue bacteria mediate synthesis of 1alpha-OHB, a steroid that is central to whole body energy and nitrogen balance in this ancient group of fishes. HQP involved in this research will gain technical skills at all levels of whole animal physiology. Studies are designed to discover the evolution of regulatory mechanisms controlling complex physiological systems in an inclusive environment that promotes the success of all individuals through community involvement, conference attendance, collaboration and publication. The research will significantly impact our understanding of the evolution of perhaps the most studied hormones in comparative endocrinology; insulin and corticosteroids. Furthermore, many species of sturgeons and elasmobranchs are under threat of extinction around the world; data generated will be applied to improve management and conservation efforts for elasmobranchs in the global aquarium trade and conservation aquaculture of sturgeons.

能量平衡的适当调节对地球上的所有生命都至关重要，并且在多细胞生物体中部分地通过释放到循环系统中的一系列激素来实现，这些激素用于控制营养物通过肠道的吸收，然后由生物体分配，储存或使用。由胰腺B细胞释放的胰岛素调节人体血糖可能是这方面研究最深入的例子。在古代鱼类中，激素如何调节营养物质的吸收、储存和/或使用在很大程度上是未知的。作为“活化石”，板鳃类（鲨鱼、冰鞋和鳐）和鲟鱼是解决我研究项目长期目标的极好模型，即了解胰岛素和皮质类固醇等激素的功能如何在脊椎动物中进化。有三个主要的研究领域，其短期目标旨在了解：1）激素释放的控制; 2）肠道营养吸收的激素调节; 3）肝脏营养加工的激素控制。主要的营养物质是葡萄糖;然而，鲟鱼的代谢组织，特别是板鳃类，表明酮在整个动物的能量平衡中也起着重要作用。建议的目标集中在调节胰岛素释放的胰岛细胞的板鳃类和鲟鱼，以及如何glucoregulating激素，如胰岛素，胰高血糖素和GLP 1的影响摄取葡萄糖在这些古老的鱼类肠道。皮质醇在鲟鱼和板鳃类特定的皮质类固醇，1 α-羟基皮质酮（1 α-OHB），在这两组鱼的肝脏中的葡萄糖和酮的加工的行动将进一步我们的理解在这些鱼类的应激反应的机制基础。板鳃类的具体研究将检查肠道微生物群落在全身氮平衡中的作用，并测试新的假设，即通过互惠关系组织细菌介导1 α-OHB的合成，1 α-OHB是一种类固醇，是这一古老鱼类群体全身能量和氮平衡的核心。参与这项研究的HQP将获得整个动物生理学各个层面的技术技能。研究旨在发现在一个包容性的环境中控制复杂生理系统的调节机制的演变，通过社区参与，会议出席，合作和出版促进所有个人的成功。这项研究将极大地影响我们对比较内分泌学中研究最多的激素的进化的理解;胰岛素和皮质类固醇。此外，世界各地许多鲟鱼和板鳃类物种面临灭绝的威胁;所产生的数据将用于在全球水族馆贸易和鲟鱼养护性水产养殖中改善对板鳃类的管理和养护工作。