Adipose tissue-derived biological signals in integrative metabolism

这项研究计划的总体目标是：1)提高脂肪(脂肪)组织中发生的基本生物学过程的基本知识；2)教育/培训这一基础科学研究领域的高素质人员(如本科生、研究生)。传统上，脂肪组织被视为脂肪形式的多余能量(卡路里)的储存库。由于脂肪细胞和免疫细胞，如巨噬细胞和T细胞的复杂组成，现在人们了解到脂肪组织在身体中还有许多其他重要的功能。特别是，脂肪组织制造和释放大量称为脂肪因子的分子，这些分子充当体内各种过程的媒介，包括炎症反应和饮食中糖和脂肪的新陈代谢。目前，我们对脂肪因子的基本生物学知之甚少，包括它们的合成是如何调节(增加/减少)的，以及它们如何在脂肪组织内的脂肪细胞和免疫细胞之间或与其他对新陈代谢重要的组织(如骨骼肌)之间发挥“通信信号”的作用。在我的实验室进行的研究表明，饮食营养物质，如脂肪酸，包括鱼油衍生的omega-3(n-3)脂肪酸、二十碳五烯酸和二十二碳六烯酸，可以调节脂肪因子，并对脂肪因子介导的细胞间通讯有有利影响，而n-6脂肪酸，如花生四烯酸，可能有相反的作用。然而，我们对脂肪酸对脂肪组织生物学影响的基本知识，以及我们对各种脂肪酸如何或通过何种机制发挥作用的确切了解是有限的。为了研究脂肪酸如何影响脂肪组织衍生的脂肪因子，以及它们随后在细胞(脂肪细胞、巨噬细胞、T细胞)和组织(脂肪组织、肌肉)之间的沟通中影响炎症和代谢反应的作用，我的实验室将进行动物实验和细胞培养。更具体地说，我的实验室已经建立了各种模拟脂肪组织生物学方面的细胞培养系统，在这些系统中，我们可以使用刺激或应激来扰乱新陈代谢过程，如炎症介质、脂多糖或限制氧气供应。利用我们已建立的系统，我们可以研究脂肪酸如何调节脂肪组织/细胞对这种压力的反应，以及这反过来如何影响其他组织，如肌肉。总体而言，这项研究将使我们能够全面了解脂肪组织中的基本生物学过程。此外，这项研究将带来关于特定脂肪酸影响的新知识，这将对对优化加拿大饮食中的脂肪酸感兴趣的食品部门具有价值。重要的是，我的研究组的学生将精通整合生理学、营养学/新陈代谢和免疫学的研究技能，这些都是基础科学研究的关键领域。

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.