Biological impact of dietary components on nutrient absorption and metabolism

维生素是人类和动物必需的微量营养素。叶酸是天然叶酸(维生素B9)的合成形式，用于强化食品、补充剂和动物饲料。叶酸/叶酸是人类和动物正常生长发育所必需的一种关键营养物质。叶酸/叶酸的吸收和代谢效率在保证人类和动物的叶酸依赖功能方面起着重要作用。当饮食摄入不足、肠道吸收减少、肝功能受损或身体需求增加时，就会发生叶酸缺乏。虽然西方食品和动物饲料中添加了叶酸，但高能量饮食或受霉菌毒素污染的主食/饲料中的某些成分可能会干扰叶酸的动态平衡，损害其细胞功能。例如，根据2000卡路里的摄入量，推荐的人类总脂肪摄入量是卡路里的20%-35%。然而，在西方国家，膳食脂肪往往占能量摄入量的40%以上。在一项初步研究中，我们观察到，给小鼠喂食高脂肪饮食(60%大卡脂肪)5周和12周会导致血液叶酸水平显著下降，即使它们摄入了足够的叶酸。这与氧化应激增加(体内自由基积聚)和肝功能受损有关。目前尚不清楚高脂肪饮食如何影响叶酸的吸收和代谢。除了营养物质外，真菌毒素(由真菌产生的毒素)不可避免地作为天然污染物存在于食物链中，可能对人类和动物有害。虽然主食和饲料中真菌毒素的最大容许水平是立法的，但它们对营养(即叶酸)吸收的影响(低于立法水平)尚不清楚。鉴于叶酸作为一种基本营养素的重要性，必须了解饮食成分如何调节其肠道吸收、细胞吸收和新陈代谢，以确保其最佳的生物学功能。在这项拟议的研究中，我们将研究(1)饮食衍生因素如何影响肠道对叶酸的吸收及其在肝脏的代谢；(2)氧化应激和细胞信号通路如何参与营养平衡。我的长期目标是开发一个研究平台，以确定饮食成分(从营养素到污染物和添加剂)如何影响营养素的生物利用率，并调查减轻饮食因素对叶酸和其他营养素吸收和代谢的负面影响是否可以优化它们在人类和动物中的生物功能。更好地了解这些影响将为政府和行业提供新的战略，以优化膳食叶酸和其他营养素的摄入量。共有10名学生(2名博士、3名硕士和5名本科生)将作为建议的NSERC发现计划的一部分进行培训。**

Vitamins are essential micronutrients for humans and animals. Folic acid is a synthetic form of the naturally occurring folate (vitamin B9) that is used in fortified foods, supplements and animal feeds. Folate/folic acid is a key nutrient essential for the normal growth and development of humans and animals. The efficiency of folate/folic acid absorption and metabolism plays an important role in ensuring folate-dependent functions in humans and animals. Folate deficiency can occur when dietary intake is inadequate, intestinal absorption is decreased, liver function is impaired or when body need is increased. Although Western foods and animal feeds are fortified with folic acid, some components in energy-dense diets or mycotoxin-contaminated staple foods/feeds may interfere with folate homeostasis and compromise its cellular function. For example, the recommended total fat intake for humans is 20-35% of kcal based on a 2,000 calorie intake. However, in Western countries, dietary fat often comprises over 40% of the energy intake. In a pilot study, we observed that feeding mice a high-fat diet (60% kcal fat) for 5 and 12 weeks caused a significant decrease in blood folate levels even though they received adequate amounts of dietary folic acid. This was associated with increased oxidative stress (free radical build-up in the body) and impaired liver function. It is not clear how high-fat diets affect folate absorption and metabolism. Aside from nutrients, mycotoxins (toxins produced by fungi) are unavoidably present in the food chain as natural contaminants, which can be harmful to humans and animals. Although the maximum tolerated levels of mycotoxins in staple foods and feeds are legislated, their impact (below the legislated levels) on nutrient (i.e. folate) absorption is not known. Given the importance of folate as an essential nutrient, it is imperative to understand how dietary components regulate its intestinal absorption, cellular uptake and metabolism to ensure its optimal biological function. In the proposed research, we will investigate (1) how dietary-derived factors influence folic acid absorption in the intestine and its metabolism in the liver; (2) how oxidative stress and cellular signaling pathways are involved in nutrient balance. My long-term goal is to develop a research platform to identify how dietary components (ranging from nutrients to contaminants and additives) affect nutrient bioavailability and to investigate whether mitigating negative influences of dietary factors on folate and other nutrient absorption and metabolism can optimize their biological functions in humans and animals. Better understanding of these effects will equip the government and industry with new strategies to optimize the intake of dietary folate and other nutrients. Total of 10 students (2 PhD, 3 MSc and 5 undergraduate) will be trained as part of the proposed NSERC Discovery program.**