Biological impact of dietary components on nutrient absorption and metabolism

膳食成分对营养吸收和代谢的生物学影响

• 批准号: RGPIN-2017-05500
• 负责人: O, Karmin
• 金额: $ 2.04万
• 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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=682121
• 关键词: Biological; impact; dietary; components; nutrient

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.**

维生素是人类和动物必需的微量营养素。叶酸是天然存在的叶酸（维生素B 9）的合成形式，用于强化食品，补充剂和动物饲料。叶酸是人类和动物正常生长和发育所必需的关键营养素。叶酸/叶酸吸收和代谢的效率在确保人类和动物的叶酸依赖性功能中起着重要作用。叶酸缺乏症可能发生在饮食摄入不足，肠道吸收减少，肝功能受损或身体需要增加时。虽然西方食品和动物饲料中添加了叶酸，但能量密集型饮食或霉菌毒素污染的主食/饲料中的某些成分可能会干扰叶酸稳态并损害其细胞功能。例如，基于2，000卡路里的摄入量，推荐的人类总脂肪摄入量为20-35%千卡。然而，在西方国家，膳食脂肪通常占能量摄入的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%千卡脂肪）5周和12周会导致血液叶酸水平显著下降，即使它们获得了足够量的膳食叶酸。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。除了营养素，真菌毒素（真菌产生的毒素）也是食物链中不可或缺的天然污染物，对人类和动物有害。虽然法定的主食和饲料中霉菌毒素的最大耐受水平，但其对营养素（即叶酸）吸收的影响（低于法定水平）尚不清楚。鉴于叶酸作为一种必需营养素的重要性，必须了解膳食成分如何调节其肠道吸收，细胞吸收和代谢，以确保其最佳生物功能。在拟议的研究中，我们将研究（1）饮食来源的因素如何影响叶酸在肠道中的吸收及其在肝脏中的代谢;（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，以确定膳食成分（从营养素到污染物和添加剂）如何影响营养素的生物利用度，并研究减轻膳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使政府和行业制定新的策略，以优化膳食叶酸和其他营养素的摄入。共有10名学生（2名博士，3名硕士和5名本科生）将接受培训，作为拟议的NSERC发现计划的一部分。