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

瘦素是一种重要的激素，参与广泛的生理过程。尽管关于瘦素在哺乳动物调节能量消耗中的作用的文献很多，但对其他脊椎动物的代谢功能知之甚少。为了更好地了解这一重要激素的进化，该奖项支持的研究将确定罗非鱼（Oreochromis mossambicus）中两种瘦素类似物（leptin A和leptin B）的代谢作用和调节，这是一种成熟的内分泌和渗透调节模型。该项目将评估与应激诱导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作用，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）作为综合内分泌应激反应的一部分的调节相互作用。除了提高瘦素生物学和脊椎动物代谢控制的知识外，该项目还将让研究生、本科生和高中生参与研究活动，重点是培养对实验设计、全动物生理学、分子和细胞生物学以及内分泌学的理解。首席研究员还将与NCSU的科学之家以及NC数学和科学教育网络大学预科项目合作，加强K-12 STEM教育，并招募代表性不足的学生进入生命科学项目。第二个外联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，以开发教学模块，以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粮食部门之一，也是动物蛋白的主要来源，对罗非鱼的应激相关能量消耗的研究可以改善养殖罗非鱼和其他鱼类的管理做法。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，使用比较硬骨鱼模型，将提供瘦素在调节变温动物代谢中的功能的详细理解。其次，这些研究将确立瘦素在介导应激反应中的关键作用。这些研究将确定硬骨鱼多种瘦素的功能和调控。此外，对两种瘦素类似物的检查可能揭示了在端骨细胞（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重要的案例研究。总的来说，这些研究将提供瘦素、新陈代谢和脊椎动物分解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和在科学会议上发表来传播。

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.