Metabolic and Immune Functions of Zinc and Lipids

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My NSERC Discovery program studies the role of dietary zinc and dietary lipids (fats) in immune cell function and metabolism. The overarching hypothesis is that zinc-finger proteins are important for understanding the molecular functions of zinc and the effects of zinc deficiency and supplementation. Molecular studies show that the finger-like areas in zinc-finger proteins are critical for their structure and function. However, my team is the first to show that dietary zinc deficiency elevates levels of a zinc-finger protein in immune cells called Lck. Elevated Lck is associated with fewer newly released T cells in the blood and spleen of Zn-deficient rats. Lck controls survival and death of T cells, however, the newly released T cells from Zn-deficient animals are not more susceptible to a type of cell death called apoptosis. We have also shown that zinc supplementation may make immune function worse in rats with excess body fat since newly reduced T cells are reduced and inflammation is increased. Thus, our research on zinc and immune function is challenging accepted ideas in the literature about zinc deficiency and supplementation, and establishing the importance of studying the effects of zinc nutrition on zinc-finger proteins in vivo. The research program also investigates the effects of dietary fats on fat cells and immune cells in the fat tissue. My team has shown that plant-based omega-3 fatty acids can reduce the number of immune cells in fat tissue and decrease the size of the fat cells which improves their function. Although fat cells can expand and shrink, they are continually replaced in fat tissue as they have a limited lifespan. Thus, we need to learn more about the remodelling of fat tissue as animals go through periods of calorie excess or calorie deficiency due to changes in food availability or physiological state. There are some newly discovered zinc-finger proteins which are important for metabolism in fat cells and for attracting immune cells into fat tissue. For the next cycle of my NSERC Discovery program we want to apply our experience with nutritional immunology and fat cell biology to determine how dietary zinc is modulating fat cell function and turnover, as well as the roles of immune cells within fat tissue. We also want to investigate how different types of dietary fat may lessen or worsen the effects of zinc deficiency or supplementation. We want to identify some new genes and metabolites that help explain how zinc regulates feed intake and metabolism during periods of calorie excess or deficiency. This research program will establish the effects of zinc nutrition and zinc status on the in vivo function of zinc-finger proteins important for the function of fat cells and immune cells. The research program will train 4 graduate students and 5 undergraduate studies. It will build capacity in Canada for fundamental research on nutrition and metabolism, and the biology of immune cells and fat cells.