2012 Annual Report
1)block cholesterol transport into cells (macrophages); and.
2)prevent oxidation of cholesterol in these cells, thereby reducing inflammation that impairs macrophage function. These researchers further determined that the phenolic acids in the serum following consumption of blueberries appear to be responsible for many of these protective effects. In summary, the present study identified mechanisms by which blueberries may be cardio-protective and further identified phenolic acids as the causative factors. 5. Distinct gene expression signatures in the rat placentation site. The placenta is the earliest maternal/fetal organ to develop in all pregnant eutherian mammals (mammals that have a placenta) and is essential for fetal development. The placenta is entrusted with a number of functions, including the transport of nutrients and gases to support fetal growth, and providing protection against maternal immune response during pregnancy. To achieve these diverse functions, the rat placenta is composed of three diverse layers containing distinctive cell types. Scientists at the Arkansas Children's Nutrition Center, in Little Rock, Arkansas, utilized sequencing techniques to study the gene expression of these layers. Sequencing-based analysis allowed discovery of small proteins at very low levels and allowed researchers to elucidate unique gene networks that orchestrate functions within these placenta compartments. Most importantly, this work provides a novel resource to understand gene expression and function in different placenta compartments. 6. Maternal obesity promotes a pro-inflammatory signature in rat uterus and blastocyst. Understanding how maternal obesity influences the developing offspring is critical in mitigating the rise in obesity. Using a model of maternal overweight at conception, researchers at the Arkansas Children's Nutrition Center in Little Rock, Arkansas studied regulation of genes in the uterus of obese pregnant rats shortly after conception. Using a technique to assay thousands of genes at one time (microarrays), these investigators discovered that pregnancy of obese rats led to accumulation of fat in the implantation site. This was accompanied with an increase in proinflammatory genes and proteins which led to biochemical changes in the developing embryo (blastocyst). These studies highlight the possibility that maternal body composition may alter the development of the offspring by influencing the milieu in which early development occurs. 7. Blueberries consumed in early life protect against adult bone loss. The effects of early diet on bone turnover (a lifelong process where mature bone tissue is removed and new bone tissue is formed) may influence how much peak bone mass is attained in individuals and the risk of osteoporosis in later life. Investigators at the Arkansas Children's Nutrition Center in Little Rock, Arkansas, have determined that blueberries fed during pre-pubertal development can enhance the formation of new bone cells (osteoblasts) and prevent them from losing activity as they age (senescence). The effect of blueberries appears to be through increases in cytoskeletal proteins (such as myosin) which control the shape of cells, and movement of other protein factors (such as Runx2) from the cytosol to the nucleus. Therefore, early blueberry consumption can influence osteoporosis risk in old age by increasing the life of bone cells, resulting in higher peak bone mass as adults. 8. Maternal obesity impairs fetal bone development. It has been suggested that the environment the fetus develops in during pregnancy may permanently alter later organ development. Investigators at the Arkansas Children's Nutrition Center in Little Rock, Arkansas, have shown that maternal obesity reduced the ability of fetal bone cell precursors to develop into mature bone cells (osteoblasts) and increased their likelihood of becoming fat cells instead. This was found to be associated with a specific modification (known as methylation) of an important gene in skeletal development (the HoxA10 gene). The effect of obesity was mimicked in cell culture by a certain type of free fatty acids (non-esterified) that increases as the level of fat tissue increases during development of obesity. These studies suggest that maternal obesity may result in permanent reductions in skeletal mass in offspring and increase fracture risk. 9. Targeting distinct breast cancer subtypes with diets. Breast cancer is a complex disease characterized by more than two dozen types of cells capable of becoming cancerous, making it extremely difficult to treat. The major challenge faced by clinicians is how to provide chemotherapy in sufficient doses that specifically target and kill mammary tumor-initiating sub-populations without eliciting side effects that dramatically impair quality of life. Using human mammary cancer cells, scientists at the Arkansas Children's Nutrition Center in Little Rock, Arkansas, found that the soy isoflavone genistein can inhibit the expansion of mammary stem/progenitor cells from well-differentiated estrogen receptor-expressing breast tumors (as well as from more invasive, non-estrogen receptor-expressing breast tumors). They further found that polyphenolic acids found in serum following consumption of blueberries, specifically hippuric acid, only targeted mammary stem/progenitor cells from the more deadly triple-negative breast tumors. These findings provide support to the role of genistein (and perhaps soy foods) and hippuric acid (and perhaps blueberries) in mammary tumor protection and raise the novel possibility of using these compounds or diet as an adjunct to standard breast cancer treatments for increased drug efficacy. 10. Formula feeding changes gene expression profiles and iron storage in liver. Although breast feeding is supported by the American Academy of Pediatrics, reports of iron deficiency in breast-fed infants are not uncommon. Investigators at the Arkansas Children's Nutrition Center in Little Rock, Arkansas, have used a neonatal pig model and a technique studying thousands of liver genes at once (called microarray technology) to show that formula feeding produces a liver gene expression signature and metabolic profile substantially different from that of breast feeding. Formula-fed piglets had lower liver iron stores, altered expression of iron-regulated genes, and lower cholesterol than breast-fed piglets. Cow's milk formula and soy formula-fed piglets differed significantly in which genes in the liver were turned on or turned off. Furthermore, genes typically regulated by estrogens were not affected by either formula. These studies suggest that metabolic responses of neonates to breast milk and formula differ significantly and that there is no evidence to suggest that soy formula has estrogenic actions in the neonatal liver.
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Ronis, M.J., Chen, Y., Shankar, K., Gomez-Acevedo, H., Cleves, M.A., Badeaux, J., Blackburn, M.L., Badger, T.M. 2011. Formula feeding alters hepatic gene expression signature, iron and cholesterol homeostasis in the neonatal pig. Physiological Genomics. 43(23):1281-1293.
Simmen, F.A., Simmen, R.C. 2011. The maternal womb: a novel target for cancer prevention in the era of the obesity pandemic?. European Journal of Cancer Prevention. 20(6):539-548.
Xie, C., Kang, J., Chen, J., Lazarenko, O.P., Ferguson, M.E., Badger, T.M., Nagarajan, S., Wu, X. 2011. Lowbush blueberries inhibit scavenger receptors CD36 and SR-A expression and attenuate foam cell formation in ApoE-deficient mice. Food and Function. 2(10):588-594.
Xie, C., Kang, J., Ferguson, M., Nagarajan, S., Badger, T.M., Wu, X. 2011. Blueberries reduce pro-inflammatory cytokine TNF-alpha and IL-6 production in mouse macrophages by inhibiting NF Kappa B activation and the MAPK pathway. Molecular Nutrition and Food Research. 55(10):1587-1591.
Shankar, K., Zhong, Y., Kang, P., Lau, F., Blackburn, M.L., Chen, J., Borengasser, S., Ronis, M.J., Badger, T.M. 2011. Maternal obesity promotes a proinflammatory signature in rat uterus and blastocyst. Journal of Endocrinology. 152(11):4158-4170.
Chen, J., Zhang, J., Lazarenko, O.P., Kang, P., Blackburn, M.L., Ronis, M.J., Badger, T.M., Shankar, K. 2012. Inhibition of fetal bone development through epigenetic down- regulation of HoxA10 in obese rats fed high fat diet. Journal of Federation of American Societies for Experimental Biology. 26(3):1131-1141.
Montales, M.E., Rahal, O., Kang, J., Rogers, T., Prior, R.L., Wu, X., Simmen, R.C. 2012. Repression of mammosphere formation of human breast cancer cells by soy isoflavone genistein and blueberry polyphenolic acids suggests diet-mediated targeting of cancer stem-like/progenitor cells. Carcinogenesis. 33(3):652-660.
Shankar, K., Zhong, Y., Kang, P., Blackburn, M.L., Soares, M.J., Badger, T.M., Gomez-Acevedo, H. 2012. Rna-seq analysis of the functional compartments within the rat placentation site. Endocrinology. 153(4):1999-2011.
Xie, C., Kang, J., Chen, J., Nagarajan, S., Badger, T.M., Wu, X. 2011. Phenolic acids are in vivo atheroprotective compounds appearing in serum of rats after blueberry consumption. Journal of Agricultural and Food Chemistry. 59(18):10381-10387.
Zhang, J., Lazarenko, O.P., Wu, X., Tong, Y., Blackburn, M.L., Gomez-Avecedo, H., Shankar, K., Badger, T.M., Ronis, M.J., Chen, J. 2012. Differential effects of short term feeding of a soy protein isolate diet and estrogen treatment on bone in the pre-pubertal rat. PLoS One. 7(4):e35736.
Ng, H., Burris, R.L., Nagarajan, S. 2011. Attenuated atherosclerotic lesions in apoe-fc gamma-chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of regulatory T cells. Journal of Immunology. 187(11):6082-6093.
Andres, A., Pivik, R.T., Casey, P., Tang, X., Badger, T.M. 2012. Developmental status of one year old infants fed breast-milk, cow's milk formula or soy formula. Pediatrics. 129(6):1134-1140.
Kang, J., Xie, C., Schauss, A.G., Kondo, M., Ou, B., Jensen, G., Wu, X. 2012. Bioactivities of acai (Euterpe precatoria mart.) fruit pulp, superior antioxidant and anti-inflammatory properties to Euterpe oleracea mart. Food Chemistry. 133(3):671-677.
Weaver, C.M., Alekel, D.L., Ward, W.E., Ronis, M.J. 2012. Flavonoid intake and bone health. Journal of Nutrition in Gerontology and Geriatrics. 31(3):239-253.
Andres, A., Shankar, K., Badger, T.M. 2012. Body fat mass of exclusively breastfed infants born to overweight mothers. Journal of the Academy of Nutrition and Dietetics. 112(7):991-995.