Regulation of folic acid absorption and metabolism

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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.