Regulation of folic acid absorption and metabolism

叶酸是一种合成形式的天然存在的叶酸，是水溶性维生素B9。叶酸用于强化食品、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功能中起着重要作用。叶酸缺乏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。虽然动物饲料和西餐都添加了叶酸，但一些饮食成分可能会干扰叶酸的吸收，损害其细胞功能。例如，以2000卡路里的摄入量为基础，建议人类总脂肪摄入量为卡路里的20-35%。然而，在西方国家，膳食脂肪通常占能量摄入的40%以上。在最近的一项研究中，我们观察到，给老鼠喂食5-12周的高脂肪食物会导致血液中叶酸水平显著下降，即使老鼠摄入了足够量的叶酸。这与氧化应激增加（体内自由基积聚）和肝功能受损有关。叶酸/叶酸在肠道的吸收和随后在肝脏（叶酸储存和代谢的主要器官）的摄取是通过叶酸转运蛋白介导的。目前尚不清楚高脂肪饮食如何影响叶酸的吸收和代谢。除营养物质外，真菌毒素（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耐受水平有法律规定，但它们对营养吸收的影响（低于法定水平）尚不清楚。在拟议的研究中，我的研究小组将(1)研究饮食来源的因素，如能量密集的食物（高脂肪）或霉菌毒素如何影响叶酸在肠道中的吸收及其在肝脏中的代谢；(2)确定氧化应激和细胞信号通路是否参与营养平衡。该研究项目将推进我们关于优化营养吸收和代谢对人类和动物生物功能影响的知识。

Folic acid is a synthetic form of the naturally occurring folate that is water soluble vitamin B9. Folic acid 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 animal feeds and Western foods are fortified with folic acid, some dietary components may interfere with folate/folic acid absorption 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 recent study, we observed that feeding mice a high-fat diet for 5-12 weeks caused a significant decrease in blood folate levels even though mice received adequate amount of dietary folic acid. This was associated with increased oxidative stress (free radical build-up in the body) and impaired liver function. Folate/folic acid absorption in the intestine and subsequent uptake in the liver (a major organ for folate storage and metabolism) are mediated through folate transporters. It is not clear how high-fat diet affects 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 absorption is not known. In the proposed research, My research team will (1) investigate how dietary-derived factors such as energy-dense food (high-fat) or mycotoxin influence folic acid absorption in the intestine and its metabolism in the liver; (2) identify whether oxidative stress and cellular signaling pathways are involved in nutrient balance. The research program will advance our knowledge pertaining to the impact of optimizing nutrients absorption and metabolism on their biological functions in humans and animals.