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于地球上的所有生命都至关重要，在多细胞生物体中，能量平衡的部分实现是通过释放到循环系统中的一系列激素来实现的，这些激素的作用是控制肠道对营养物质的吸收，然后进行分配和储存。或被生物体使用。通过胰腺 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尚未被探索。作为“活化石”，软骨鱼（鲨鱼、鳐鱼和鳐鱼）和鲟鱼是实现我的研究计划的长期目标的绝佳模型，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。短期目标包括三个主要研究领域，旨在了解：1）控制激素释放； 2）肠道营养吸收的激素调节； 3）肝脏对营养处理的激素控制。主要的营养素是葡萄糖；然而，鲟鱼，特别是软骨鱼类的代谢组织表明，酮在整个动物的能量平衡中也发挥着重要作用。拟议的目标集中于软骨鱼和鲟鱼胰岛细胞中胰岛素释放的调节，以及胰岛素、胰高血糖素和 GLP 1 等葡萄糖调节激素如何影响这些古老鱼类肠道对葡萄糖的吸收。鲟鱼中的皮质醇和软骨鱼类特异性皮质类固醇 1α-羟基皮质酮 (1α-OHB) 对两组鱼类肝脏中葡萄糖和酮的处理的作用将进一步加深我们对这些鱼类应激反应机制基础的理解。鱼。 Elasmobranch 的具体研究将检验肠道微生物群落在全身氮平衡中所起的作用，并测试新的假设，即组织细菌通过互惠关系介导 1alpha-OHB 的合成，1alpha-OHB 是一种对全身能量和氮平衡至关重要的类固醇。古老的鱼类群。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。研究旨在发现在包容性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进化的理解；胰岛素和皮质类固醇。此外，世界各地许多种鲟鱼和软骨鱼正面临灭绝的威胁。生成的数据将用于改善全球水族馆贸易和鲟鱼保护水产养殖中软骨鱼的管理和保护工作。