ABSORPTION AND METABOLISM OF ESSENTIAL MINERAL NUTRIENTS IN CHILDREN
Children's Nutrition Research Center
2012 Annual Report
1a. Objectives (from AD-416):
The overall goal of our research is to develop nutritionally enhanced plant foods that provide increased nutrient bioavailability and absorption in children. Ultimately, this plant food research in combination with mineral nutrition research in children will allow researchers to provide guidance regarding food intake and fortification, specifically related to iron, zinc, Vitamin C and calcium. Specific objectives of this research include: 1) use genetic, molecular, and physiological approaches to define the role of specific genes and gene products in the acquisition and whole-organism partitioning of minerals (iron, zinc, Vitamin C, calcium, and magnesium) and other factors that inhibit or promote absorption of these minerals in plant foods; 2) Conduct animal and human feeding studies to determine mineral bioavailability of the nutritionally enhanced crops; 3) develop new, cost-effective methods for the intrinsic labeling of plant foods for use in nutrient bioavailability studies; 4) determine the absorption of dietary calcium, magnesium, iron, and zinc in children and the influence of other nutrients and dietary factors on the absorption; 5) (deleted due to resignation of investigator); 6) determine the effect of dietary components on the upregulation of intestinal iron transporter genes in human models; 7) characterize dynamic indices of bone formation by quantitative histomorphometry and micro computed tomography in 7 mouse models; 8) quantitate specific gene expression in calvarial osteoblasts derived from mouse models; and 9) determine the effects of hormone ablation, iron loading, ASC feeding and plant derived antioxidants on bone parameters in vivo. These efforts will expand our capabilities for assessing the absorption and metabolism of various plant-derived minerals and phytochemicals and will provide novel information directly useful to government, industry and the consumer related to dietary requirements. The generation of new bioavailability data for various plant-derived nutrients will be established and such data will have global application and provide a strong basis for evidence-based nutritional recommendations to be developed.
1b. Approach (from AD-416):
These research studies will utilize diverse plant species, human cell culture systems, or human subjects. CNRC scientists will focus on characterizing plant genes and gene products that are involved with mineral transport in the plant, with a focus on iron, zinc, calcium, and magnesium. We will use specifically manipulated transgenic lines, various plant mutants, or unique plant genotypes to assess the impact of altered genes on mineral transport and storage throughout various plant tissues. In order to facilitate studies of bioavailability of plant-based nutrients, we will develop new, cost-effective methods for the intrinsic, stable-isotopic labeling of plant foods, by testing different hydroponic strategies and altered timings of isotope application to the plants. Food-based factors associated with the dietary delivery of the essential minerals calcium, iron, and zinc will be investigated using human in vitro cell culture and human subject-based experiments. We will conduct a controlled trial of vitamin D supplementation to assess the effects of vitamin D status on calcium absorption in small children. We will evaluate different types of whole diets (lacto-ovo vegetarian) on iron status and the effects of differing intakes of zinc on zinc and copper absorption. We will determine if benefits previously seen for prebiotic fibers in enhancing calcium absorption also occur for iron absorption. Low abundance stable isotopes of each element will be used to track absorption in each of these human studies. In vitro cell culture models will seek to identify the genetic basis for iron and zinc absorption in intestinal cells, by monitoring mineral absorption in combination with the differential expression of various metal transporter genes. We will explore the roles of aldose reductase and aldehyde reductase in modulating oxidative stress in cells, as well as their separate role in providing the starting substrates for the ascorbate synthesis pathway. Ultimately we will have a better understanding of the role of vitamin C in our diet.
3. Progress Report:
Significant research progress was accomplished during the year. To review the progress, please refer to project 6250-51000-051-10S (Project 1) and 6250-51000-051-20S (Project 2).
Zhai, J., Jeong, D.-H., De Paoli, E., Park, S., Rosen, B.D., Li, Y., Gonzalez, A.J., Yan, Z., Kitto, S.L., Grusak, M.A., Jackson, S.A., Stacey, G., Cook, D.R., Green, P.J., Sherrier, D.J., Meyers, B.C. 2011. MicroRNAs as master regulators of the plant NB-LRR defense gene family via the production of phased, trans-acting siRNAs. Genes and Development. 25:2540-2553.
Nakata, P.A. 2011. The oxalic acid biosynthetic activity of Burkholderia mallei is encoded by a single locus. Microbiological Research. 166(7):531-538.
Abrams, S.A. 2011. Vitamin D supplementation during pregnancy. Journal of Bone and Mineral Research. 26(10):2338-2340.
Abrams, S.A. 2012. Abnormalities of serum calcium and magnesium. In: Cloheryt, J.P., Eichenwald, E.C., Hansen, A.R., Stark, A.R., editors. Manual of Neonatal Care, 7th edition. Philadelphia, PA: Lippincott Williams & Wilkins. p. 297-303.
Abrams, S.A. 2011. Calcium and vitamin D requirements for optimal bone mass during adolescence. Current Opinion in Clinical Nutrition and Metabolic Care. 14(6):605-609.
Pammi, M., Abrams, S.A. 2011. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolotis in preterm infants. Cochrane Database Systematic Reviews. Issue 10:CD007137.
Nakata, P.A. 2012. Engineering calcium oxalate crystal formation in Arabidopsis. Plant Cell Physiology. 53(7):1275-1282.
Abrams, S.A. 2012. Osteopenia and bone health in patients with intestinal failure. In: Duggan, C.P., Gura, K.M., Jaksic, T., editors. Clinical Management of Intestinal Failure. Boca Raton, FL:CRC Press. p. 271-281.
Tiosano, D., Hadad, S., Chen, Z., Nemirovsky, A., Gepstein, V., Militianu, D., Weisman, Y., Abrams, S.A. 2011. Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets. Journal of Clinical Endocrinology and Metabolism. 96(12):3701-3709.
Armas, L.A., Rafferty, K., Hospattankar, A., Abrams, S.A., Heaney, R.P. 2011. Chronic dietary fiber supplementation with wheat dextrin does not inhibit calcium and magnesium absorption in premenopausal and postmenopausal women. Journal of International Medical Research. 39(5):1824-1833.
Prentice, A.M., Doherty, C.P., Abrams, S.A., Cox, S.E., Atkinson, S.H., Verhoef, H., Armitage, A.E., Drakesmith, H. 2012. Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children. Blood. 119(8):1922-1928.
Dauber, A., Nguyen, T.T., Sochett, E., Cole, D.E., Horst, R., Abrams, S.A., Carpenter, T.O., Hirschhorn, J.N. 2012. Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia. Journal of Clinical Endocrinology and Metabolism. 97:E268-E274.
Nakata, P.A. 2012. Plant calcium oxalate crystal formation, function, and its impact on human health. Frontiers in Biology. 7(3):254-266.
Abrams, S.A., Hawthorne, K.M., Rogers, S.P., Hicks, P.D., Carpenter, T.O. 2012. Effects of ethnicity and vitamin D supplementation on vitamin D status and changes in bone mineral content in infants. BMC Pediatrics. 12:6.
Luo, B., Nakata, P.A. 2012. A set of GFP organelle marker lines for intracellular localization studies in Medicago truncatula. Plant Science. 188-189:19-24.
Tang, G., Hu, Y., Yin, S., Wang, Y., Dallal, G.E., Grusak, M.A., Russell, R.M. 2012. Beta-carotene in Golden Rice is as good as beta-carotene in oil at providing vitamin A to children. American Journal of Clinical Nutrition. 96(3):658-664.
Yu, B., Wang, J., Suter, P.M., Russell, R.M., Grusak, M.A., Wang, Y., Wang, Z., Yin, S., Tang, G. 2012. Spirulina is an effective dietary source of zeaxanthin to humans. British Journal of Nutrition. 108(4):611-619.
Pammi, M., Abrams, S.A. 2011. Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates. Cochrane Database Systematic Reviews. Issue 10:CD007138.
Kwon, S.J., Brown, A.F., Hu, J., Mcgee, R.J., Watt, C., Kisha, T.J., Timmerman-Vaughan, G., Grusak, M.A., Mcphee, K., Coyne, C.J. 2012. Genetic diversity, population structure and genome-wide marker-trait association analysis of the USDA pea (Pisum sativum L.) core collection. Genes and Genomics. 10.1007/s13258-011-0213-z.
Undurraga, S.F., Santos, M.P., Paez-Valencia, J., Yang, H., Hepler, P.K., Facanha, A.R., Hirschi, K.D., Gaxiola, R.A. 2012. Arabidopsis sodium dependent and independent phenotypes triggered by H+-PPase up-regulation are SOS1 dependent. Plant Science. 183:96-105.
Rajabi, A., Booth, S., Peterson, J., Choi, S., Suttie, J., Shea, M., Miao, B., Grusak, M.A., Fu, X. 2012. Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats. Journal of Nutrition. 142(5):841-845.
Hirschi, K.D. 2012. New foods for thought. Trends in Plant Science. 17(3):123-125.
Punshon, T., Hirschi, K.D., Yang, J., Lanzirotti, A., Guerinot, M. 2011. The role of CAX1 and CAX3 in elemental distribution and abundance in Arabidopsis seed. Plant Physiology. 158(1):352-362.
Rosen, C.J., Abrams, S.A., Aloia, J.F., Brannon, P.M., Clinton, S.K., Durazo-Arvizu, R.A., Gallagher, J.C., Gallo, R.L., Jones, G., Kovacs, C.S., Manson, J.E., Mayne, S.T., Ross, A.C., Shapses, S.A., Taylor, C.L. 2012. IOM committee members respond to Endocrine Society vitamin D guideline. Journal of Clinical Endocrinology and Metabolism. 97(4):1146-1152.
Abrams, S.A. 2012. Vitamin D requirements of children: "All my life's a circle". Nutrition Reviews. 70(4):201-206.
Abrams, S.A. 2012. Osteopenia (metabolic bone disease) of prematurity. In: Cloherty, J.P., Eichenwald, E.C., Hansen, A.R., Stark, A.R., editors. Manual of Neonatal Care. 7th edition. Philadelphia, PA: Lippincott Williams & Wilkins. p. 762-766.
Abrams, S.A., Hawthorne, K.M. 2012. Bone Health in Children. Boca Raton:CRC Press Taylor & Francis Group. 221 p.