Function and Regulation of Leptin in Mediating Stress-induced Energy Expenditure

瘦素在介导压力引起的能量消耗中的功能和调节

• 批准号: 1457040
• 负责人: Russell Borski
• 金额: $ 63.11万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1457040&HistoricalAwards=false
• 关键词: Function; Regulation; Leptin; Mediating; Stress

Leptin is an important hormone involved in a wide range of physiological processes. Despite a wealth of literature regarding the role of leptin in regulating energy expenditure in mammals, much less is known about the metabolic functions in other vertebrates. To better understand the evolution of this important hormone, the studies supported by this award will identify the metabolic action(s) and regulation of two leptin paralogs (Leptin A and Leptin B) in the tilapia (Oreochromis mossambicus), a well-established endocrine and osmoregulatory model. The project will assess the metabolic and endocrine responses associated with stress-induced leptin signaling, functionally evaluate the metabolic effects of two leptins, and identify mechanisms which elicit the leptin response. Further, these studies will evaluate regulatory interactions of leptin with other stress-induced metabolic hormones (e.g. catecholamines, glucocorticoids) as part of the integrated endocrine stress response. In addition to advancing knowledge of leptin biology and control of metabolism in vertebrates, the project will incorporate graduate, undergraduate and high school students in research activities with a focus on developing an understanding of experimental designs, whole animal physiology, molecular and cell biology and endocrinology. The Principal Investigator will also work with the Science House at NCSU, and the NC Mathematics and Science Education Network Pre-College Program, to enhance K-12 STEM education and the recruitment of under-represented students into life sciences programs. A second outreach component will be provided through the Nature Research Center at the NC Museum of Natural Sciences (Daily Planet Broadcast) to develop teaching modules to foster greater public interest in science and the biology of fishes. Studies of stress related energy expenditure in tilapia, one of the fastest growing food sectors and a prominent source of animal protein worldwide, can improve management practices for culturing this fish and others.This project will make two key advances toward understanding leptin biology in vertebrates. First, using a comparative teleost model a detailed understanding of the function(s) of leptin in regulating metabolism in ectotherms will be provided. Secondly, these studies will establish a critical role for leptin in mediating stress responses. These studies will determine the function and regulation of multiple leptins in teleost fishes. Moreover, examination of two leptin paralogs may reveal sub- or neo-functionalization of a major cytokine hormone following the teleostean (3R) genome duplication event, providing an important case study for understanding divergent gene fates. Collectively, these studies will provide a fundamental link between leptin, metabolism and catabolic stress in vertebrates. Results from the studies will be disseminated through publication in peer-reviewed journals and through presentations at scientific meetings.

瘦素是一种重要的激素，参与多种生理过程。尽管有大量关于瘦素在哺乳动物能量消耗调节中的作用的文献，但对其他脊椎动物的代谢功能知之甚少。为了更好地了解这种重要激素的进化，该奖项支持的研究将确定两个瘦素类似物(瘦素A和瘦素B)在罗非鱼中的代谢作用(S)和调节，罗非鱼是一个成熟的内分泌和渗透压调节模型。该项目将评估与应激诱导的瘦素信号相关的代谢和内分泌反应，从功能上评估两种瘦素的代谢效应，并确定引发瘦素反应的机制。此外，这些研究将评估瘦素与其他应激诱导的代谢激素(如儿茶酚胺、糖皮质激素)的调节相互作用，作为综合内分泌应激反应的一部分。除了增进瘦素生物学和脊椎动物新陈代谢控制的知识外，该项目还将吸收研究生、本科生和高中生参与研究活动，重点是发展对实验设计、整体动物生理学、分子和细胞生物学以及内分泌学的理解。首席调查员还将与NCSU的科学之家以及NC数学和科学教育网络大学前计划合作，以加强K-12 STEM教育和生命科学计划招收代表不足的学生。第二个外展部分将通过北卡罗来纳州自然科学博物馆的自然研究中心(每日星球广播)提供，以开发教学单元，培养公众对科学和鱼类生物学的更大兴趣。罗非鱼是世界上增长最快的食物部门之一，也是动物蛋白的重要来源。对罗非鱼应激相关能量消耗的研究，可以改善这种鱼和其他鱼的养殖管理实践。该项目将在理解脊椎动物瘦素生物学方面取得两个关键进展。首先，使用比较硬骨模型将提供对瘦素在外胚层新陈代谢调节中的功能(S)的详细理解。其次，这些研究将确立瘦素在调节应激反应中的关键作用。这些研究将确定多种瘦素在硬骨鱼中的功能和调节。此外，对两个瘦素同源基因的研究可能揭示硬骨动物(3R)基因组复制事件后一种主要细胞因子激素的亚功能化或新功能化，为理解不同的基因命运提供了一个重要的案例研究。总而言之，这些研究将提供脊椎动物瘦素、代谢和分解代谢应激之间的基本联系。这些研究的结果将通过在同行评议的期刊上发表以及在科学会议上发表报告来传播。