Adipose tissue-derived biological signals in integrative metabolism

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The overall goals of this research proposal are to 1) advance fundamental knowledge of the basic biological processes that occur in adipose (fat) tissue and 2) educate/train highly qualified personnel (e.g. undergraduate, graduate students) in this area of basic science research. Traditionally, adipose tissue was viewed as simply a storage depot for excess energy (Calories) in lipid form. It is now understood that adipose tissue has many other important functions in the body, owing to its complex composition of fat cells and immune cells, such as macrophages and T cells. In particular, adipose tissue makes and releases numerous molecules called adipokines that act as mediators of various processes in the body, including inflammatory responses and metabolism of dietary sugars and fats. Currently, we know very little about the basic biology of adipokines, including how their synthesis is modulated (increased/decreased) and how they function as “communication signals” between fat cells and immune cells within adipose tissue, or with other tissues that are important to metabolism, such as skeletal muscle. Research conducted in my lab has shown that dietary nutrients, such as fatty acids, including fish oil-derived omega-3 (n-3) fatty acids, eicosapentaenoic acid and docosahexaenoic acid, can modulate adipokines and have beneficial effects on adipokine-mediated cell-cell communication, while n-6 fatty acids, such as arachidonic acid, may have opposing effects. However, our basic knowledge of fatty acid effects on adipose tissue biology and our understanding of exactly how, or the mechanisms by which, various fatty acids exert their effects is limited. To study how fatty acids influence adipose tissue-derived adipokines and their subsequent role in communication between cells (fat cells, macrophages, T cells) and tissues (adipose tissue, muscle) that influences inflammatory and metabolic responses, my lab will perform experiments with animals and cell culture. More specifically, my lab has established various cell culture systems that mimic aspects of adipose tissue biology, wherein we can disrupt metabolic processes using stimuli or stress, such as the inflammatory agent, LPS, or restricted oxygen availability. Using our established systems allows us to study how fatty acids can modulate adipose tissue/cell response to such stress and how this, in turn, influences other tissues, such as muscle. Overall, this research will enable us to establish a comprehensive picture of basic biological processes in adipose tissue. As well, this research will lead to new knowledge on the effect of specific fatty acids that will have value for food sectors interested in optimizing fatty acids in the Canadian diet. Importantly, students in my research group will become proficient in research skills that integrate physiology, nutrition/metabolism and immunology, key areas of basic science research.