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

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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.