Hormonal Regulation of Feeding, Metabolism, Growth and Reproduction in Fish

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The long-term goal of my discovery research program is to create new knowledge through the characterization of novel hormones that regulate metabolism, growth and reproduction in fish. In the past five years, we discovered the biological actions of numerous hormones. Among them, nesfatin-1 and nesfatin-1-like peptide (Nlp) are two multifunctional peptides that were found to regulate feeding, metabolism, growth and reproduction in fish. In addition, three growth factors that regulate feeding and metabolism were characterized. While nesfatin-1 and Nlp have multiple biological actions, whether they are essential to maintain fish physiology is unknown. The mechanism of action of nesfatin-1 and Nlp is poorly understood. Whether growth factors regulate reproduction and growth in fish is unclear. This proposal builds on our original discoveries, and it is a logical and feasible extension of our research to date. It aims to conduct the next set of studies to fill several knowledge gaps on these important regulators in fish. Under objective 1, using genetic tools, we will delete nesfatin-1 and Nlp genes in zebrafish and determine how critical these two peptides are in maintaining metabolic homeostasis, growth and reproduction. It is anticipated that the loss of one or both peptides lead to disturbed metabolism, growth and reproduction. In objective 2, the mechanism of action of nesfatin-1 and Nlp will also be determined using pharmacological agents and genetic tools that can tease out specific receptors and pathways. We believe that a cell surface receptor and dedicated intracellular signals are important for nesfatin-1 and Nlp action. Objective 3 will explore the role of growth factors in regulating growth and reproduction will be studied by measuring the effects of these peptides on gamete development, ovarian follicle maturation, growth, body weight and major hormones that regulate these processes. We expect these previously uncharacterized growth factors to stimulate both growth and reproduction and the hormonal milieu that supports it in zebrafish. The novel fundamental knowledge created though this research will help redefine and update our current understanding of fish biology. It could be beneficial by helping learn how these hormones regulate important processes in other species including domestic animals. The outcomes of this program are expected to help develop new strategies to enhance fish growth and reproduction in aquaculture, thus contributing to sustainability and food security. This research provides remarkable opportunities for training the next generation of young researchers, especially women and those underrepresented in science. They will contribute to the pool of highly qualified personnel required by Canada's workforce and economy. Overall, the proposed research program will generate considerable new knowledge while contributing indirectly, yet significantly to the economy and sustainability efforts in Canada.