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.

对能量平衡的适当调节对地球上的所有生命至关重要，并且在多细胞生物体中通过释放到循环系统中的一套激素在多细胞生物中实现，这些激素可控制肠道的养分，然后是生物体的分布，储存或使用。通过胰腺B细胞释放的胰岛素对人类血糖的调节可能是最深入的研究例子。在古老的鱼类中，激素如何调节摄取，储存和/或使用营养物质在很大程度上没有探索。由于“活化石”弹性分支（鲨鱼，溜冰鞋和射线）和st鱼是解决我的研究计划的长期目标的绝佳模型，以了解胰岛素中的胰岛素和皮质类固醇等激素的功能。研究的三个主要领域具有短期目标，目的是了解：1）控制激素释放； 2）整个肠道养分吸收的荷尔蒙调节； 3）肝脏对养分加工的荷尔蒙控制。感兴趣的主要营养素是葡萄糖。然而，st鱼，尤其是弹性分支的代谢组织表明酮在整个动物的能量平衡中也起着重要作用。提出的目标集中在调节弹性和st鱼的胰岛胰岛细胞中的胰岛素释放，以及胰岛素，胰高血糖素和GLP 1等葡萄糖细胞激素如何影响这些古老鱼类中葡萄糖的吸收。皮质醇在st鱼和弹性蛋白酶特异性皮质类固醇中的作用，1alpha-羟基皮质酮（1α-OHB），对两组鱼类中肝脏在肝脏中处理葡萄糖和酮的处理将进一步我们在这些鱼类机械响应的基础上的理解。 Elasmobranch具体研究将研究肠道微生物群落在全身氮平衡中发挥的作用，并检验了新的假设，即通过相互关系的关系，组织细菌介导了1Alpha-OHB的合成，这种类固醇是这种古老的鱼类中全体能量和氮平衡的核心。参与这项研究的HQP将在整个动物生理学的各个层面上获得技术技能。研究旨在发现在包容性环境中控制复杂生理系统的监管机制的演变，该环境通过社区参与，会议出勤，合作和出版物来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，许多种类的st鱼和弹性分支在世界范围内受到灭绝的威胁。生成的数据将用于改善全球水族馆贸易和st鱼保护水产养殖中的弹性分支的管理和保护工作。