Mechanisms of Glucocorticoid Action on Adipose Tissue Metabolism

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Glucocorticoids (GCs), or stress hormones, play a role in regulating energy flux and structural changes in fat tissue. Studies have identified a strong link between high levels of GCs and inappropriate accumulation of fat in mammalians. Although white (stores excess energy) and brown (expends excess energy as heat) fat tissues function in very different ways, they have evolved to become very dynamic organs that specialize in regulating whole-body energy balance. We know that chronic and high levels of GCs increase the distribution and amount of fat tissue, but we still do not understand how GCs cause these abnormalities. Previously, I demonstrated that activated GCs were increased within centralized depots in rats treated with GCs and fed a high-fat diet. I also showed that specific GC inhibitors do not change GC-induced central fat accumulation, despite lower levels of activated GCs, indicating that mechanisms behind GC activators may be dispensable for fat storage or metabolism. However, to date, this question has not been resolved. Consequently, the long-term objective of my research is to better understand how fat is influenced by hormonal control, which in-turn affects how fat tissue expands and grows. I will study fat biogenesis through the response of white and brown fat to conditions of high levels of GCs and how it relates to energy balance. I am particularly interested in this area of research due to emerging evidence demonstrating the importance of fat for integral communication between bodily systems. In the next 5 years I will pursue 3 short-term goals: 1. To investigate how GCs increase fat loading into fat tissue 2. To explore specific pathways used in GC signaling in fat tissue in mice models 3. To identify hormones that are influenced by GC action in fat tissue I will address these goals by performing experiments in cell culture, primary fat models, as well as mouse models. Ultimately, this work will provide novel understanding of underlying mechanisms of GC action that will augment comprehension of fat biology, such as expansion and hormone regulation that govern energy balance. This research will train both BSc and MSc students. Scientific studies in my laboratory will provide trainees with hands-on research experience and science knowledge in the fields of nutrition, physiology, and metabolism that will be translatable to a variety of scientific careers. My research plan will offer a challenging and stimulating environment for all personnel and allow them to gain highly sought after skills, such as conceptualizing complex problems, performing hypothesis driven research, developing effective time management, refining proper data analysis, and communicating effectively through presentations and publications. Accordingly, this research program will provide new and impactful insights into fundamental aspects of the biogenesis of fat, and will offer excellent scientific training to the personnel involved in this research.