Metabolic and Immune Functions of Zinc and Lipids

锌和脂质的代谢和免疫功能

• 批准号: RGPIN-2019-05880
• 负责人: Taylor, Carla
• 金额: $ 3.42万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714655
• 关键词: Metabolic; Immune; Functions; Zinc; Lipids

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.

我的 NSERC 发现计划研究膳食锌和膳食脂质（脂肪）在免疫细胞功能和代谢中的作用。总体假设是锌指蛋白对于理解锌的分子功能以及锌缺乏和补充的影响非常重要。分子研究表明，锌指蛋白中的指状区域对其结构和功能至关重要。然而，我的团队第一个证明饮食中的锌缺乏会提高免疫细胞中一种名为 Lck 的锌指蛋白的水平。 Lck 升高与缺锌大鼠的血液和脾脏中新释放的 T 细胞较少有关。 Lck 控制 T 细胞的存活和死亡，然而，缺锌动物新释放的 T 细胞并不更容易受到称为细胞凋亡的细胞死亡类型的影响。我们还发现，补充锌可能会使体内脂肪过多的大鼠的免疫功能恶化，因为新减少的 T 细胞减少，炎症增加。因此，我们对锌和免疫功能的研究挑战了文献中有关锌缺乏和补充的公认观点，并确立了研究锌营养对体内锌指蛋白影响的重要性。 该研究项目还研究了膳食脂肪对脂肪组织中的脂肪细胞和免疫细胞的影响。我的团队已经证明，植物性 omega-3 脂肪酸可以减少脂肪组织中免疫细胞的数量，并减小脂肪细胞的大小，从而改善其功能。尽管脂肪细胞可以扩张和收缩，但它们在脂肪组织中不断被替换，因为它们的寿命有限。因此，我们需要更多地了解动物由于食物供应或生理状态的变化而经历热量过剩或热量不足时期时脂肪组织的重塑。 有一些新发现的锌指蛋白对于脂肪细胞的新陈代谢和吸引免疫细胞进入脂肪组织非常重要。在我的 NSERC 发现计划的下一个周期中，我们希望运用我们在营养免疫学和脂肪细胞生物学方面的经验来确定膳食锌如何调节脂肪细胞功能和周转，以及脂肪组织内免疫细胞的作用。我们还想研究不同类型的膳食脂肪如何减轻或恶化锌缺乏或补充剂的影响。 我们希望确定一些新的基因和代谢物，以帮助解释锌如何在热量过剩或缺乏期间调节采食量和新陈代谢。 该研究计划将确定锌营养和锌状态对锌指蛋白体内功能的影响，锌指蛋白对脂肪细胞和免疫细胞的功能很重要。该研究项目将培养4名研究生和5名本科生。它将建设加拿大营养和新陈代谢以及免疫细胞和脂肪细胞生物学基础研究的能力。